Targeted inhibition of STATs and IRFs as a potential treatment strategy in cardiovascular disease

Oncotarget

Volumn 7, Issue 30, 2016, Pages 48788-48812

  Szelag, Malgorzata ^a   Piaszyk Borychowska, Anna ^a   Plens Galaska, Martyna ^a   Wesoly, Joanna ^a   Bluyssen, Hans A R ^a  

^a ADAM MICKIEWICZ UNIVERSITY   (Poland)

Author keywords

In silico modeling; IRF; STAT; Therapeutic strategy; Vascular inflammation

Indexed keywords

3 (6 BROMO 2 PYRIDINYL) 2 CYANO N (1 PHENYLETHYL)ACRYLAMIDE; 5 CHLORO N2 [1 (5 FLUORO 2 PYRIMIDINYL)ETHYL] N4 (5 METHYL 1H PYRAZOL 3 YL) 2,4 PYRIMIDINEDIAMINE; CAPSAICIN; CASEIN KINASE II; COP9 SIGNALOSOME; CRYPTOTANSHINONE; CUCURBITACIN; CURCUMIN; FEDRATINIB; GAMMA INTERFERON; GAMMA INTERFERON INDUCIBLE PROTEIN 10; INTERFERON CONSENSUS SEQUENCE BINDING PROTEIN; INTERFERON REGULATORY FACTOR; MACROPHAGE INFLAMMATORY PROTEIN 3BETA; MYELOID DIFFERENTIATION FACTOR 88; PATTERN RECOGNITION RECEPTOR; PIMOZIDE; PRAVASTATIN; PROTEIN SH2; RESVERATROL; RUXOLITINIB; STAT PROTEIN; STAT1 PROTEIN; STAT2 PROTEIN; STAT3 PROTEIN; TOCILIZUMAB; TOFACITINIB; TRYPTOPHAN; VASCULAR CELL ADHESION MOLECULE 1; ALPHA INTERFERON; HYPOCHOLESTEROLEMIC AGENT; IL6 PROTEIN, HUMAN; INTERLEUKIN 6; TLR4 PROTEIN, HUMAN; TOLL LIKE RECEPTOR 4;

ADAPTIVE IMMUNITY; ALLERGIC ASTHMA; ALZHEIMER DISEASE; ATHEROGENESIS; ATHEROSCLEROSIS; ATHEROSCLEROTIC PLAQUE; BINDING AFFINITY; BRAIN CANCER; BURNING MOUTH SYNDROME; CARDIOVASCULAR DISEASE; CEREBROVASCULAR ACCIDENT; CEREBROVASCULAR DISEASE; CHRONIC OBSTRUCTIVE LUNG DISEASE; DERMATITIS; DIMERIZATION; DNA BINDING; HEAD AND NECK CANCER; HEART INFARCTION; HUMAN; HUMAN IMMUNODEFICIENCY VIRUS INFECTION; HYPERTENSION; INFLAMMATION; INNATE IMMUNITY; ISCHEMIC HEART DISEASE; KIDNEY ARTERY STENOSIS; LIVER CELL CARCINOMA; LUNG CARCINOMA; MALIGNANT NEOPLASTIC DISEASE; MELANOMA; MEMORY DISORDER; MIGRAINE; MOLECULAR INTERACTION; MULTIPLE SCLEROSIS; MYELOFIBROSIS; NECK PAIN; NON INSULIN DEPENDENT DIABETES MELLITUS; OBESITY; OVARY POLYCYSTIC DISEASE; PERIPHERAL NEUROPATHY; PERIPHERAL OCCLUSIVE ARTERY DISEASE; POLYCYTHEMIA VERA; PROTEIN DEGRADATION; PROTEIN DOMAIN; PROTEIN EXPRESSION; PROTEIN FUNCTION; PROTEIN PHOSPHORYLATION; PROTEIN PROTEIN INTERACTION; PROTEIN STRUCTURE; PROTEIN TARGETING; PSORIASIS; PULMONARY HYPERTENSION; REVIEW; RHEUMATOID ARTHRITIS; RHINITIS; SCHIZOPHRENIA; SOLID TUMOR; STOMACH CANCER; THROMBOCYTHEMIA; ANTAGONISTS AND INHIBITORS; CLINICAL TRIAL (TOPIC); DRUG EFFECTS; METABOLISM; MOLECULAR DOCKING; MOLECULARLY TARGETED THERAPY; PATHOLOGY; PHOSPHORYLATION; PRECLINICAL STUDY; PROCEDURES; SIGNAL TRANSDUCTION; TRENDS;

ANTICHOLESTEREMIC AGENTS; ATHEROSCLEROSIS; CLINICAL TRIALS AS TOPIC; DRUG EVALUATION, PRECLINICAL; HUMANS; INFLAMMATION; INTERFERON REGULATORY FACTORS; INTERFERON-ALPHA; INTERFERON-GAMMA; INTERLEUKIN-6; MOLECULAR DOCKING SIMULATION; MOLECULAR TARGETED THERAPY; PHOSPHORYLATION; PLAQUE, ATHEROSCLEROTIC; SIGNAL TRANSDUCTION; STAT TRANSCRIPTION FACTORS; TOLL-LIKE RECEPTOR 4;

EID: 84982847721     PISSN: None     EISSN: 19492553     Source Type: Journal    
DOI: 10.18632/oncotarget.9195     Document Type: Review

References (190)

1. Mathers CD and Loncar D. Projections of global mortality and burden of disease from 2002 to 2030. PLoS medicine. 2006; 3:e442.
2. Sikorski K, Czerwoniec A, Bujnicki JM, Wesoly J and Bluyssen HA. STAT1 as a novel therapeutical target in pro-atherogenic signal integration of IFNgamma, TLR4 and IL-6 in vascular disease. Cytokine & growth factor reviews. 2011; 22:211-219.
3. Hack CE and Zeerleder S. The endothelium in sepsis: source of and a target for inflammation. Critical care medicine. 2001; 29:S21-27.
4. Lusis AJ. Atherosclerosis. Nature. 2000; 407:233-241.
5. Allahverdian S, Chehroudi AC, McManus BM, Abraham T and Francis GA. Contribution of intimal smooth muscle cells to cholesterol accumulation and macrophage-like cells in human atherosclerosis. Circulation. 2014; 129:1551-1559.
6. Robertson AK and Hansson GK. T cells in atherogenesis: for better or for worse? Arteriosclerosis, thrombosis, and vascular biology. 2006; 26:2421-2432.
7. Yilmaz A, Lochno M, Traeg F, Cicha I, Reiss C, Stumpf C, Raaz D, Anger T, Amann K, Probst T, Ludwig J, Daniel WG and Garlichs CD. Emergence of dendritic cells in rupture-prone regions of vulnerable carotid plaques. Atherosclerosis. 2004; 176:101-110.
8. Bobryshev YV and Lord RS. Co-accumulation of dendritic cells and natural killer T cells within rupture-prone regions in human atherosclerotic plaques. The journal of histochemistry and cytochemistry. 2005; 53:781-785.
9. Libby P. Inflammation in atherosclerosis. Nature. 2002; 420:868-874.
10. Hansson GK, Robertson AK and Soderberg-Naucler C. Inflammation and atherosclerosis. Annual review of pathology. 2006; 1:297-329.
11. Levy DE and Darnell JE, Jr. Stats: transcriptional control and biological impact. Nature reviews Molecular cell biology. 2002; 3:651-662.
12. Tamura T, Yanai H, Savitsky D and Taniguchi T. The IRF family transcription factors in immunity and oncogenesis. Annual review of immunology. 2008; 26:535-584.
13. Grote K, Luchtefeld M and Schieffer B. JANUS under stress-role of JAK/STAT signaling pathway in vascular diseases. Vascular pharmacology. 2005; 43:357-363.
14. Sun H and Wang Y. Interferon regulatory factors in heart: stress response beyond inflammation. Hypertension. 2014; 63:663-664.
15. Ehret GB, Reichenbach P, Schindler U, Horvath CM, Fritz S, Nabholz M and Bucher P. DNA binding specificity of different STAT proteins. Comparison of in vitro specificity with natural target sites. The Journal of biological chemistry. 2001; 276:6675-6688.
16. Bonham AJ, Wenta N, Osslund LM, Prussin AJ, 2nd, Vinkemeier U and Reich NO. STAT1:DNA sequencedependent binding modulation by phosphorylation, protein:protein interactions and small-molecule inhibition. Nucleic acids research. 2013; 41:754-763.
17. Khan KD, Shuai K, Lindwall G, Maher SE, Darnell JE, Jr. and Bothwell AL. Induction of the Ly-6A/E gene by interferon alpha/beta and gamma requires a DNA element to which a tyrosine-phosphorylated 91-kDa protein binds. Proceedings of the National Academy of Sciences of the United States of America. 1993; 90:6806-6810.
18. Horvath CM, Wen Z and Darnell JE, Jr. A STAT protein domain that determines DNA sequence recognition suggests a novel DNA-binding domain. Genes & development. 1995; 9:984-994.
19. Sadowski HB, Shuai K, Darnell JE, Jr. and Gilman MZ. A common nuclear signal transduction pathway activated by growth factor and cytokine receptors. Science. 1993; 261:1739-1744.
20. Zhong Z, Wen Z and Darnell JE, Jr. Stat3: a STAT family member activated by tyrosine phosphorylation in response to epidermal growth factor and interleukin-6. Science. 1994; 264:95-98.
21. Hengerer B, Lindholm D, Heumann R, Ruther U, Wagner EF and Thoenen H. Lesion-induced increase in nerve growth factor mRNA is mediated by c-fos. Proceedings of the National Academy of Sciences of the United States of America. 1990; 87:3899-3903.
22. Leong PL, Andrews GA, Johnson DE, Dyer KF, Xi S, Mai JC, Robbins PD, Gadiparthi S, Burke NA, Watkins SF and Grandis JR. Targeted inhibition of Stat3 with a decoy oligonucleotide abrogates head and neck cancer cell growth. Proceedings of the National Academy of Sciences of the United States of America. 2003; 100:4138-4143.
23. Nehyba J, Hrdlickova R, Burnside J and Bose HR, Jr. A novel interferon regulatory factor (IRF), IRF-10, has a unique role in immune defense and is induced by the v-Rel oncoprotein. Molecular and cellular biology. 2002; 22:3942-3957.
24. Escalante CR, Yie J, Thanos D and Aggarwal AK. Structure of IRF-1 with bound DNA reveals determinants of interferon regulation. Nature. 1998; 391:103-106.
25. Sharf R, Azriel A, Lejbkowicz F, Winograd SS, Ehrlich R and Levi BZ. Functional domain analysis of interferon consensus sequence binding protein (ICSBP) and its association with interferon regulatory factors. The Journal of biological chemistry. 1995; 270:13063-13069.
26. Darnell JE, Jr., Kerr IM and Stark GR. Jak-STAT pathways and transcriptional activation in response to IFNs and other extracellular signaling proteins. Science. 1994; 264:1415-1421.
27. Sharf R, Meraro D, Azriel A, Thornton AM, Ozato K, Petricoin EF, Larner AC, Schaper F, Hauser H and Levi BZ. Phosphorylation events modulate the ability of interferon consensus sequence binding protein to interact with interferon regulatory factors and to bind DNA. The Journal of biological chemistry. 1997; 272:9785-9792.
28. Meraro D, Hashmueli S, Koren B, Azriel A, Oumard A, Kirchhoff S, Hauser H, Nagulapalli S, Atchison ML and Levi BZ. Protein-protein and DNA-protein interactions affect the activity of lymphoid-specific IFN regulatory factors. Journal of immunology. 1999; 163:6468-6478.
29. Penninger JM, Sirard C, Mittrucker HW, Chidgey A, Kozieradzki I, Nghiem M, Hakem A, Kimura T, Timms E, Boyd R, Taniguchi T, Matsuyama T and Mak TW. The interferon regulatory transcription factor IRF-1 controls positive and negative selection of CD8+ thymocytes. Immunity. 1997; 7:243-254.
30. Lin R and Hiscott J. A role for casein kinase II phosphorylation in the regulation of IRF-1 transcriptional activity. Molecular and cellular biochemistry. 1999; 191:169-180.
31. Cohen H, Azriel A, Cohen T, Meraro D, Hashmueli S, Bech-Otschir D, Kraft R, Dubiel W and Levi BZ. Interaction between interferon consensus sequence-binding protein and COP9/signalosome subunit CSN2 (Trip15). A possible link between interferon regulatory factor signaling and the COP9/signalosome. The Journal of biological chemistry. 2000; 275:39081-39089.
32. Birnbaum MJ, van Zundert B, Vaughan PS, Whitmarsh AJ, van Wijnen AJ, Davis RJ, Stein GS and Stein JL. Phosphorylation of the oncogenic transcription factor interferon regulatory factor 2 (IRF2) in vitro and in vivo. Journal of cellular biochemistry. 1997; 66:175-183.
33. Bailey CM, Abbott DE, Margaryan NV, Khalkhali-Ellis Z and Hendrix MJ. Interferon regulatory factor 6 promotes cell cycle arrest and is regulated by the proteasome in a cell cycle-dependent manner. Molecular and cellular biology. 2008; 28:2235-2243.
34. Biswas PS, Gupta S, Chang E, Song L, Stirzaker RA, Liao JK, Bhagat G and Pernis AB. Phosphorylation of IRF4 by ROCK2 regulates IL-17 and IL-21 production and the development of autoimmunity in mice. The Journal of clinical investigation. 2010; 120:3280-3295.
35. Lopez-Pelaez M, Lamont DJ, Peggie M, Shpiro N, Gray NS and Cohen P. Protein kinase IKKbeta-catalyzed phosphorylation of IRF5 at Ser462 induces its dimerization and nuclear translocation in myeloid cells. Proceedings of the National Academy of Sciences of the United States of America. 2014; 111:17432-17437.
36. Xu XH, Shah PK, Faure E, Equils O, Thomas L, Fishbein MC, Luthringer D, Xu XP, Rajavashisth TB, Yano J, Kaul S and Arditi M. Toll-like receptor-4 is expressed by macrophages in murine and human lipid-rich atherosclerotic plaques and upregulated by oxidized LDL. Circulation. 2001; 104:3103-3108.
37. Methe H, Kim JO, Kofler S, Weis M, Nabauer M and Koglin J. Expansion of circulating Toll-like receptor 4-positive monocytes in patients with acute coronary syndrome. Circulation. 2005; 111:2654-2661.
38. Michelsen KS, Wong MH, Shah PK, Zhang W, Yano J, Doherty TM, Akira S, Rajavashisth TB and Arditi M. Lack of Toll-like receptor 4 or myeloid differentiation factor 88 reduces atherosclerosis and alters plaque phenotype in mice deficient in apolipoprotein E. Proceedings of the National Academy of Sciences of the United States of America. 2004; 101:10679-10684.
39. Cani PD, Amar J, Iglesias MA, Poggi M, Knauf C, Bastelica D, Neyrinck AM, Fava F, Tuohy KM, Chabo C, Waget A, Delmee E, Cousin B, Sulpice T, Chamontin B, Ferrieres J, et al. Metabolic endotoxemia initiates obesity and insulin resistance. Diabetes. 2007; 56:1761-1772.
40. Amar J, Burcelin R, Ruidavets JB, Cani PD, Fauvel J, Alessi MC, Chamontin B and Ferrieres J. Energy intake is associated with endotoxemia in apparently healthy men. Am J Clin Nutr. 2008; 87:1219-1223.
41. Szeto CC, Kwan BC, Chow KM, Lai KB, Chung KY, Leung CB and Li PK. Endotoxemia is related to systemic inflammation and atherosclerosis in peritoneal dialysis patients. Clin J Am Soc Nephrol. 2008; 3:431-436.
42. Laugerette F, Vors C, Peretti N and Michalski MC. Complex links between dietary lipids, endogenous endotoxins and metabolic inflammation. Biochimie. 2011; 93:39-45.
43. Lu Z, Zhang X, Li Y, Jin J and Huang Y. TLR4 antagonist reduces early-stage atherosclerosis in diabetic apolipoprotein E-deficient mice. J Endocrinol. 2013; 216:61-71.
44. Cole JE, Georgiou E and Monaco C. The expression and functions of toll-like receptors in atherosclerosis. Mediators Inflamm. 2010; 2010:393946.
45. Kanellakis P, Agrotis A, Kyaw TS, Koulis C, Ahrens I, Mori S, Takahashi HK, Liu K, Peter K, Nishibori M and Bobik A. High-mobility group box protein 1 neutralization reduces development of diet-induced atherosclerosis in apolipoprotein e-deficient mice. Arteriosclerosis, thrombosis, and vascular biology. 2011; 31:313-319.
46. Erridge C. The roles of Toll-like receptors in atherosclerosis. Journal of innate immunity. 2009; 1:340-349.
47. Kawai T and Akira S. The role of pattern-recognition receptors in innate immunity: update on Toll-like receptors. Nature immunology. 2010; 11:373-384.
48. Schindler C, Levy DE and Decker T. JAK-STAT signaling: from interferons to cytokines. The Journal of biological chemistry. 2007; 282:20059-20063.
49. Wesoly J, Szweykowska-Kulinska Z and Bluyssen HA. STAT activation and differential complex formation dictate selectivity of interferon responses. Acta biochimica Polonica. 2007; 54:27-38.
50. McLaren JE and Ramji DP. Interferon gamma: a master regulator of atherosclerosis. Cytokine & growth factor reviews. 2009; 20:125-135.
51. Levy Z, Rachmani R, Trestman S, Dvir A, Shaish A, Ravid M and Harats D. Low-dose interferon-alpha accelerates atherosclerosis in an LDL receptor-deficient mouse model. Eur J Intern Med. 2003; 14:479-483.
52. Goossens P, Gijbels MJ, Zernecke A, Eijgelaar W, Vergouwe MN, van der Made I, Vanderlocht J, Beckers L, Buurman WA, Daemen MJ, Kalinke U, Weber C, Lutgens E and de Winther MP. Myeloid type I interferon signaling promotes atherosclerosis by stimulating macrophage recruitment to lesions. Cell metabolism. 2010; 12:142-153.
53. Noels H and Weber C. Catching up with important players in atherosclerosis: type I interferons and neutrophils. Current opinion in lipidology. 2011; 22:144-145.
54. Tellides G, Tereb DA, Kirkiles-Smith NC, Kim RW, Wilson JH, Schechner JS, Lorber MI and Pober JS. Interferon-gamma elicits arteriosclerosis in the absence of leukocytes. Nature. 2000; 403:207-211.
55. Leon ML and Zuckerman SH. Gamma interferon: a central mediator in atherosclerosis. Inflammation research. 2005; 54:395-411.
56. Schuett H, Luchtefeld M, Grothusen C, Grote K and Schieffer B. How much is too much? Interleukin-6 and its signalling in atherosclerosis. Thromb Haemost. 2009; 102:215-222.
57. Huber SA, Sakkinen P, Conze D, Hardin N and Tracy R. Interleukin-6 exacerbates early atherosclerosis in mice. Arteriosclerosis, thrombosis, and vascular biology. 1999; 19:2364-2367.
58. Ridker PM, Rifai N, Stampfer MJ and Hennekens CH. Plasma concentration of interleukin-6 and the risk of future myocardial infarction among apparently healthy men. Circulation. 2000; 101:1767-1772.
59. Schrader LI, Kinzenbaw DA, Johnson AW, Faraci FM and Didion SP. IL-6 deficiency protects against angiotensin II induced endothelial dysfunction and hypertrophy. Arteriosclerosis, thrombosis, and vascular biology. 2007; 27:2576-2581.
60. Protogerou AD, Zampeli E, Fragiadaki K, Stamatelopoulos K, Papamichael C and Sfikakis PP. A pilot study of endothelial dysfunction and aortic stiffness after interleukin-6 receptor inhibition in rheumatoid arthritis. Atherosclerosis. 2011; 219:734-736.
61. Levy DE, Kessler DS, Pine R and Darnell JE, Jr. Cytoplasmic activation of ISGF3, the positive regulator of interferon-alpha-stimulated transcription, reconstituted in vitro. Genes & development. 1989; 3:1362-1371.
62. Yuan J, Wegenka UM, Lutticken C, Buschmann J, Decker T, Schindler C, Heinrich PC and Horn F. The signalling pathways of interleukin-6 and gamma interferon converge by the activation of different transcription factors which bind to common responsive DNA elements. Molecular and cellular biology. 1994; 14:1657-1668.
63. Guschin D, Rogers N, Briscoe J, Witthuhn B, Watling D, Horn F, Pellegrini S, Yasukawa K, Heinrich P, Stark GR and et al. A major role for the protein tyrosine kinase JAK1 in the JAK/STAT signal transduction pathway in response to interleukin-6. EMBO J. 1995; 14:1421-1429.
64. Li X, Leung S, Qureshi S, Darnell JE, Jr. and Stark GR. Formation of STAT1-STAT2 heterodimers and their role in the activation of IRF-1 gene transcription by interferonalpha. The Journal of biological chemistry. 1996; 271:5790-5794.
65. Sikorski K, Chmielewski S, Olejnik A, Wesoly JZ, Heemann U, Baumann M and Bluyssen H. STAT1 as a central mediator of IFNgamma and TLR4 signal integration in vascular dysfunction. Jak-Stat. 2012; 1:241-249.
66. Jones BW, Means TK, Heldwein KA, Keen MA, Hill PJ, Belisle JT and Fenton MJ. Different Toll-like receptor agonists induce distinct macrophage responses. Journal of leukocyte biology. 2001; 69:1036-1044.
67. Decker T, Muller M and Stockinger S. The yin and yang of type I interferon activity in bacterial infection. Nature reviews Immunology. 2005; 5:675-687.
68. O'Neill LA and Bowie AG. The family of five: TIRdomain-containing adaptors in Toll-like receptor signalling. Nature reviews Immunology. 2007; 7:353-364.
69. Honda K, Takaoka A and Taniguchi T. Type I interferon [corrected] gene induction by the interferon regulatory factor family of transcription factors. Immunity. 2006; 25:349-360.
70. Schroder K, Sweet MJ and Hume DA. Signal integration between IFNgamma and TLR signalling pathways in macrophages. Immunobiology. 2006; 211:511-524.
71. Hu X, Chen J, Wang L and Ivashkiv LB. Crosstalk among Jak-STAT, Toll-like receptor, and ITAM-dependent pathways in macrophage activation. Journal of leukocyte biology. 2007; 82:237-243.
72. Hu X, Chakravarty SD and Ivashkiv LB. Regulation of interferon and Toll-like receptor signaling during macrophage activation by opposing feedforward and feedback inhibition mechanisms. Immunological reviews. 2008; 226:41-56.
73. Hu X and Ivashkiv LB. Cross-regulation of signaling pathways by interferon-gamma: implications for immune responses and autoimmune diseases. Immunity. 2009; 31:539-550.
74. Chmielewski S, Olejnik A, Sikorski K, Pelisek J, Blaszczyk K, Aoqui C, Nowicka H, Zernecke A, Heemann U, Wesoly J, Baumann M and Bluyssen HA. STAT1-dependent signal integration between IFNgamma and TLR4 in vascular cells reflect pro-atherogenic responses in human atherosclerosis. PloS one. 2014; 9:e113318.
75. Ohmori Y and Hamilton TA. The interferon-stimulated response element and a kappa B site mediate synergistic induction of murine IP-10 gene transcription by IFNgamma and TNF-alpha. Journal of immunology. 1995; 154:5235-5244.
76. Collins T, Read MA, Neish AS, Whitley MZ, Thanos D and Maniatis T. Transcriptional regulation of endothelial cell adhesion molecules: NF-kappa B and cytokine-inducible enhancers. FASEB J. 1995; 9:899-909.
77. Pietila TE, Veckman V, Lehtonen A, Lin R, Hiscott J and Julkunen I. Multiple NF-kappaB and IFN regulatory factor family transcription factors regulate CCL19 gene expression in human monocyte-derived dendritic cells. Journal of immunology. 2007; 178:253-261.
78. Liu J and Ma X. Interferon regulatory factor 8 regulates RANTES gene transcription in cooperation with interferon regulatory factor-1, NF-kappaB, and PU. 1. The Journal of biological chemistry. 2006; 281:19188-19195.
79. Pine R. Convergence of TNFalpha and IFNgamma signalling pathways through synergistic induction of IRF-1/ISGF-2 is mediated by a composite GAS/kappaB promoter element. Nucleic acids research. 1997; 25:4346-4354.
80. Chon SY, Hassanain HH and Gupta SL. Cooperative role of interferon regulatory factor 1 and p91 (STAT1) response elements in interferon-gamma-inducible expression of human indoleamine 2, 3-dioxygenase gene. The Journal of biological chemistry. 1996; 271:17247-17252.
81. Brucet M, Marques L, Sebastian C, Lloberas J and Celada A. Regulation of murine Tap1 and Lmp2 genes in macrophages by interferon gamma is mediated by STAT1 and IRF-1. Genes and immunity. 2004; 5:26-35.
82. Garner JM, Fan M, Yang CH, Du Z, Sims M, Davidoff AM and Pfeffer LM. Constitutive activation of signal transducer and activator of transcription 3 (STAT3) and nuclear factor kappaB signaling in glioblastoma cancer stem cells regulates the Notch pathway. The Journal of biological chemistry. 2013; 288:26167-26176.
83. Yu H, Pardoll D and Jove R. STATs in cancer inflammation and immunity: a leading role for STAT3. Nature reviews Cancer. 2009; 9:798-809.
84. Grivennikov SI and Karin M. Dangerous liaisons: STAT3 and NF-kappaB collaboration and crosstalk in cancer. Cytokine & growth factor reviews. 2010; 21:11-19.
85. Kesanakurti D, Chetty C, Rajasekhar Maddirela D, Gujrati M and Rao JS. Essential role of cooperative NF-kappaB and Stat3 recruitment to ICAM-1 intronic consensus elements in the regulation of radiation-induced invasion and migration in glioma. Oncogene. 2013; 32:5144-5155.
86. Sikorski K, Wesoly J and Bluyssen HA. Data mining of atherosclerotic plaque transcriptomes predicts STAT1-dependent inflammatory signal integration in vascular disease. International journal of molecular sciences. 2014; 15:14313-14331.
87. Agrawal S, Febbraio M, Podrez E, Cathcart MK, Stark GR and Chisolm GM. Signal transducer and activator of transcription 1 is required for optimal foam cell formation and atherosclerotic lesion development. Circulation. 2007; 115:2939-2947.
88. Lim WS, Timmins JM, Seimon TA, Sadler A, Kolodgie FD, Virmani R and Tabas I. Signal transducer and activator of transcription-1 is critical for apoptosis in macrophages subjected to endoplasmic reticulum stress in vitro and in advanced atherosclerotic lesions in vivo. Circulation. 2008; 117:940-951.
89. Kirchmer MN, Franco A, Albasanz-Puig A, Murray J, Yagi M, Gao L, Dong ZM and Wijelath ES. Modulation of vascular smooth muscle cell phenotype by STAT-1 and STAT-3. Atherosclerosis. 2014; 234:169-175.
90. Torella D, Curcio A, Gasparri C, Galuppo V, De Serio D, Surace FC, Cavaliere AL, Leone A, Coppola C, Ellison GM and Indolfi C. Fludarabine prevents smooth muscle proliferation in vitro and neointimal hyperplasia in vivo through specific inhibition of STAT-1 activation. American journal of physiology Heart and circulatory physiology. 2007; 292:H2935-2943.
91. Manea A, Tanase LI, Raicu M and Simionescu M. Jak/STAT signaling pathway regulates nox1 and nox4-based NADPH oxidase in human aortic smooth muscle cells. Arteriosclerosis, thrombosis, and vascular biology. 2010; 30:105-112.
92. Lagor WR, Fields DW, Bauer RC, Crawford A, Abt MC, Artis D, Wherry EJ and Rader DJ. Genetic manipulation of the ApoF/Stat2 locus supports an important role for type I interferon signaling in atherosclerosis. Atherosclerosis. 2014; 233:234-241.
93. Dutzmann J, Daniel JM, Bauersachs J, Hilfiker-Kleiner D and Sedding DG. Emerging translational approaches to target STAT3 signalling and its impact on vascular disease. Cardiovascular research. 2015; 106:365-374.
94. Zhou X, Li D, Yan W and Li W. Pravastatin prevents aortic atherosclerosis via modulation of signal transduction and activation of transcription 3 (STAT3) to attenuate interleukin-6 (IL-6) action in ApoE knockout mice. International journal of molecular sciences. 2008; 9:2253-2264.
95. Yang XP, Irani K, Mattagajasingh S, Dipaula A, Khanday F, Ozaki M, Fox-Talbot K, Baldwin WM, 3rd and Becker LC. Signal transducer and activator of transcription 3alpha and specificity protein 1 interact to upregulate intercellular adhesion molecule-1 in ischemic-reperfused myocardium and vascular endothelium. Arteriosclerosis, thrombosis, and vascular biology. 2005; 25:1395-1400.
96. Kleemann R, Verschuren L, Morrison M, Zadelaar S, van Erk MJ, Wielinga PY and Kooistra T. Antiinflammatory, anti-proliferative and anti-atherosclerotic effects of quercetin in human in vitro and in vivo models. Atherosclerosis. 2011; 218:44-52.
97. Wessely R, Hengst L, Jaschke B, Wegener F, Richter T, Lupetti R, Paschalidis M, Schomig A, Brandl R and Neumann FJ. A central role of interferon regulatory factor-1 for the limitation of neointimal hyperplasia. Human molecular genetics. 2003; 12:177-187.
98. Jiang DS, Li L, Huang L, Gong J, Xia H, Liu X, Wan N, Wei X, Zhu X, Chen Y, Chen X, Zhang XD and Li H. Interferon regulatory factor 1 is required for cardiac remodeling in response to pressure overload. Hypertension. 2014; 64:77-86.
99. Caso JR, Pradillo JM, Hurtado O, Lorenzo P, Moro MA and Lizasoain I. Toll-like receptor 4 is involved in brain damage and inflammation after experimental stroke. Circulation. 2007; 115:1599-1608.
100. Zhang SM, Gao L, Zhang XF, Zhang R, Zhu LH, Wang PX, Tian S, Yang D, Chen K, Huang L, Zhang XD and Li H. Interferon regulatory factor 8 modulates phenotypic switching of smooth muscle cells by regulating the activity of myocardin. Molecular and cellular biology. 2014; 34:400-414.
101. Doring Y, Soehnlein O, Drechsler M, Shagdarsuren E, Chaudhari SM, Meiler S, Hartwig H, Hristov M, Koenen RR, Hieronymus T, Zenke M, Weber C and Zernecke A. Hematopoietic interferon regulatory factor 8-deficiency accelerates atherosclerosis in mice. Arteriosclerosis, thrombosis, and vascular biology. 2012; 32:1613-1623.
102. Leonard D, Svenungsson E, Sandling JK, Berggren O, Jonsen A, Bengtsson C, Wang C, Jensen-Urstad K, Granstam SO, Bengtsson AA, Gustafsson JT, Gunnarsson I, Rantapaa-Dahlqvist S, Nordmark G, Eloranta ML, Syvanen AC, et al. Coronary heart disease in systemic lupus erythematosus is associated with interferon regulatory factor-8 gene variants. Circulation Cardiovascular genetics. 2013; 6:255-263.
103. Khallou-Laschet J, Varthaman A, Fornasa G, Compain C, Gaston AT, Clement M, Dussiot M, Levillain O, Graff-Dubois S, Nicoletti A and Caligiuri G. Macrophage plasticity in experimental atherosclerosis. PloS one. 2010; 5:e8852.
104. Xu H, Zhu J, Smith S, Foldi J, Zhao B, Chung AY, Outtz H, Kitajewski J, Shi C, Weber S, Saftig P, Li Y, Ozato K, Blobel CP, Ivashkiv LB and Hu X. Notch-RBP-J signaling regulates the transcription factor IRF8 to promote inflammatory macrophage polarization. Nature immunology. 2012; 13:642-650.
105. Jiang DS, Wei X, Zhang XF, Liu Y, Zhang Y, Chen K, Gao L, Zhou H, Zhu XH, Liu PP, Bond Lau W, Ma X, Zou Y, Zhang XD, Fan GC and Li H. IRF8 suppresses pathological cardiac remodelling by inhibiting calcineurin signalling. Nature communications. 2014; 5:3303.
106. Miklossy G, Hilliard TS and Turkson J. Therapeutic modulators of STAT signalling for human diseases. Nature reviews Drug discovery. 2013; 12:611-629.
107. Kortylewski M and Nechaev S. Cancer therapy using oligonucleotide-based STAT3 inhibitors: will they deliver? Therapeutic delivery. 2014; 5:239-242.
108. Szelag M, Wesoly J and Bluyssen HA. Advances in peptidic and peptidomimetic-based approaches to inhibit STAT signaling in human diseases. Curr Protein Pept Sci. 2016; 17:135-146.
109. Turkson J and Jove R. STAT proteins: novel molecular targets for cancer drug discovery. Oncogene. 2000; 19:6613-6626.
110. Song H, Wang R, Wang S and Lin J. A low-molecularweight compound discovered through virtual database screening inhibits Stat3 function in breast cancer cells. Proceedings of the National Academy of Sciences of the United States of America. 2005; 102:4700-4705.
111. Miyoshi K, Takaishi M, Nakajima K, Ikeda M, Kanda T, Tarutani M, Iiyama T, Asao N, DiGiovanni J and Sano S. Stat3 as a therapeutic target for the treatment of psoriasis: a clinical feasibility study with STA-21, a Stat3 inhibitor. J Invest Dermatol. 2011; 131:108-117.
112. Park JS, Kwok SK, Lim MA, Kim EK, Ryu JG, Kim SM, Oh HJ, Ju JH, Park SH, Kim HY and Cho ML. STA-21, a promising STAT-3 inhibitor that reciprocally regulates Th17 and Treg cells, inhibits osteoclastogenesis in mice and humans and alleviates autoimmune inflammation in an experimental model of rheumatoid arthritis. Arthritis Rheumatol. 2014; 66:918-929.
113. Schust J, Sperl B, Hollis A, Mayer TU and Berg T. Stattic: a small-molecule inhibitor of STAT3 activation and dimerization. Chem Biol. 2006; 13:1235-1242.
114. Johnson AW, Kinzenbaw DA, Modrick ML and Faraci FM. Small-molecule inhibitors of signal transducer and activator of transcription 3 protect against angiotensin II-induced vascular dysfunction and hypertension. Hypertension. 2013; 61:437-442.
115. Spitzner M, Roesler B, Bielfeld C, Emons G, Gaedcke J, Wolff HA, Rave-Frank M, Kramer F, Beissbarth T, Kitz J, Wienands J, Ghadimi BM, Ebner R, Ried T and Grade M. STAT3 inhibition sensitizes colorectal cancer to chemoradiotherapy in vitro and in vivo. Int J Cancer. 2014; 134:997-1007.
116. Matsuno K, Masuda Y, Uehara Y, Sato H, Muroya A, Takahashi O, Yokotagawa T, Furuya T, Okawara T, Otsuka M, Ogo N, Ashizawa T, Oshita C, Tai S, Ishii H, Akiyama Y, et al. Identification of a New Series of STAT3 Inhibitors by Virtual Screening. ACS Med Chem Lett. 2010; 1:371-375.
117. Ashizawa T, Miyata H, Ishii H, Oshita C, Matsuno K, Masuda Y, Furuya T, Okawara T, Otsuka M, Ogo N, Asai A and Akiyama Y. Antitumor activity of a novel small molecule STAT3 inhibitor against a human lymphoma cell line with high STAT3 activation. International journal of oncology. 2011; 38:1245-1252.
118. Oh DY, Lee SH, Han SW, Kim MJ, Kim TM, Kim TY, Heo DS, Yuasa M, Yanagihara Y and Bang YJ. Phase I Study of OPB-31121, an Oral STAT3 Inhibitor, in Patients with Advanced Solid Tumors. Cancer Res Treat. 2015; 47:607-615.
119. Hayakawa F, Sugimoto K, Harada Y, Hashimoto N, Ohi N, Kurahashi S and Naoe T. A novel STAT inhibitor, OPB-31121, has a significant antitumor effect on leukemia with STAT-addictive oncokinases. Blood Cancer J. 2013; 3:e166.
120. Kim MJ, Nam HJ, Kim HP, Han SW, Im SA, Kim TY, Oh DY and Bang YJ. OPB-31121, a novel small molecular inhibitor, disrupts the JAK2/STAT3 pathway and exhibits an antitumor activity in gastric cancer cells. Cancer Lett. 2013; 335:145-152.
121. Sakurai M, Nishio M, Yamamoto K, Okuda T, Kawano K and Ohnuki T. TMC-264, a novel inhibitor of STAT6 activation produced by Phoma sp. TC 1674. J Antibiot (Tokyo). 2003; 56:513-519.
122. Nakano T, Inoue H, Fukuyama S, Matsumoto K, Matsumura M, Tsuda M, Matsumoto T, Aizawa H and Nakanishi Y. Niflumic acid suppresses interleukin-13-induced asthma phenotypes. Am J Respir Crit Care Med. 2006; 173:1216-1221.
123. Muller J, Sperl B, Reindl W, Kiessling A and Berg T. Discovery of chromone-based inhibitors of the transcription factor STAT5. Chembiochem. 2008; 9:723-727.
124. Chiba Y, Todoroki M, Nishida Y, Tanabe M and Misawa M. A novel STAT6 inhibitor AS1517499 ameliorates antigen-induced bronchial hypercontractility in mice. Am J Respir Cell Mol Biol. 2009; 41:516-524.
125. Zhou XX, Gao PJ and Sun BG. Pravastatin attenuates interferon-gamma action via modulation of STAT1 to prevent aortic atherosclerosis in apolipoprotein E-knockout mice. Clin Exp Pharmacol Physiol. 2009; 36:373-379.
126. Lee BJ, Kim YJ, Cho DH, Sohn NW and Kang H. Immunomodulatory effect of water extract of cinnamon on anti-CD3-induced cytokine responses and p38, JNK, ERK1/2, and STAT4 activation. Immunopharmacol Immunotoxicol. 2011; 33:714-722.
127. Nelson EA, Walker SR, Weisberg E, Bar-Natan M, Barrett R, Gashin LB, Terrell S, Klitgaard JL, Santo L, Addorio MR, Ebert BL, Griffin JD and Frank DA. The STAT5 inhibitor pimozide decreases survival of chronic myelogenous leukemia cells resistant to kinase inhibitors. Blood. 2011; 117:3421-3429.
128. Bar-Natan M, Nelson EA, Walker SR, Kuang Y, Distel RJ and Frank DA. Dual inhibition of Jak2 and STAT5 enhances killing of myeloproliferative neoplasia cells. Leukemia. 2012; 26:1407-1410.
129. Lee HK, Seo IA, Shin YK, Park JW, Suh DJ and Park HT. Capsaicin inhibits the IL-6/STAT3 pathway by depleting intracellular gp130 pools through endoplasmic reticulum stress. Biochem Biophys Res Commun. 2009; 382:445-450.
130. Yang CL, Liu YY, Ma YG, Xue YX, Liu DG, Ren Y, Liu XB, Li Y and Li Z. Curcumin blocks small cell lung cancer cells migration, invasion, angiogenesis, cell cycle and neoplasia through Janus kinase-STAT3 signalling pathway. PloS one. 2012; 7:e37960.
131. Shin DS, Kim HN, Shin KD, Yoon YJ, Kim SJ, Han DC and Kwon BM. Cryptotanshinone inhibits constitutive signal transducer and activator of transcription 3 function through blocking the dimerization in DU145 prostate cancer cells. Cancer research. 2009; 69:193-202.
132. Shakibaei M, Harikumar KB and Aggarwal BB. Resveratrol addiction: to die or not to die. Molecular nutrition & food research. 2009; 53:115-128.
133. Sperl B, Seifert MH and Berg T. Natural product inhibitors of protein-protein interactions mediated by Src-family SH2 domains. Bioorg Med Chem Lett. 2009; 19:3305-3309.
134. Trecul A, Morceau F, Dicato M and Diederich M. Dietary compounds as potent inhibitors of the signal transducers and activators of transcription (STAT) 3 regulatory network. Genes & nutrition. 2012; 7:111-125.
135. Deng J, Grande F and Neamati N. Small molecule inhibitors of Stat3 signaling pathway. Current cancer drug targets. 2007; 7:91-107.
136. Lavecchia MJ, Diez RP and Colinas PA. A combined theoretical and spectroscopic study of 4, 6-di-O-acetyl-2, 3-dideoxy-D-erythro-hex-2-enopyranosyl sulfamide: a novel glycosyl carbonic anhydrase IX inhibitor. Carbohydr Res. 2011; 346:442-448.
137. Debnath B, Xu S and Neamati N. Small molecule inhibitors of signal transducer and activator of transcription 3 (Stat3) protein. Journal of medicinal chemistry. 2012; 55:6645-6668.
138. Szelag M, Czerwoniec A, Wesoly J and Bluyssen HA. Identification of STAT1 and STAT3 specific inhibitors using comparative virtual screening and docking validation. PloS one. 2015; 10:e0116688.
139. Lin L, Hutzen B, Li PK, Ball S, Zuo M, DeAngelis S, Foust E, Sobo M, Friedman L, Bhasin D, Cen L, Li C and Lin J. A novel small molecule, LLL12, inhibits STAT3 phosphorylation and activities and exhibits potent growthsuppressive activity in human cancer cells. Neoplasia. 2010; 12:39-50.
140. Bill MA, Nicholas C, Mace TA, Etter JP, Li C, Schwartz EB, Fuchs JR, Young GS, Lin L, Lin J, He L, Phelps M, Li PK and Lesinski GB. Structurally modified curcumin analogs inhibit STAT3 phosphorylation and promote apoptosis of human renal cell carcinoma and melanoma cell lines. PloS one. 2012; 7:e40724.
141. Capiralla H, Vingtdeux V, Zhao H, Sankowski R, Al-Abed Y, Davies P and Marambaud P. Resveratrol mitigates lipopolysaccharide-and Abeta-mediated microglial inflammation by inhibiting the TLR4/NF-kappaB/STAT signaling cascade. Journal of neurochemistry. 2012; 120:461-472.
142. Szelag M, Sikorski K, Czerwoniec A, Szatkowska K, Wesoly J and Bluyssen HA. In silico simulations of STAT1 and STAT3 inhibitors predict SH2 domain cross-binding specificity. European journal of pharmacology. 2013; 720:38-48.
143. Iwamura T, Yoneyama M, Yamaguchi K, Suhara W, Mori W, Shiota K, Okabe Y, Namiki H and Fujita T. Induction of IRF-3/-7 kinase and NF-kappaB in response to doublestranded RNA and virus infection: common and unique pathways. Genes Cells. 2001; 6:375-388.
144. Ali S and Kukolj G. Interferon regulatory factor 3-independent double-stranded RNA-induced inhibition of hepatitis C virus replicons in human embryonic kidney 293 cells. J Virol. 2005; 79:3174-3178.
145. Hartman AL, Dover JE, Towner JS and Nichol ST. Reverse genetic generation of recombinant Zaire Ebola viruses containing disrupted IRF-3 inhibitory domains results in attenuated virus growth in vitro and higher levels of IRF-3 activation without inhibiting viral transcription or replication. J Virol. 2006; 80:6430-6440.
146. Ren G, Cui K, Zhang Z and Zhao K. Division of labor between IRF1 and IRF2 in regulating different stages of transcriptional activation in cellular antiviral activities. Cell Biosci. 2015; 5:17.
147. Choo A, Palladinetti P, Holmes T, Basu S, Shen S, Lock RB, O'Brien TA, Symonds G and Dolnikov A. siRNA targeting the IRF2 transcription factor inhibits leukaemic cell growth. International journal of oncology. 2008; 33:175-183.
148. Bi X, Hameed M, Mirani N, Pimenta EM, Anari J and Barnes BJ. Loss of interferon regulatory factor 5 (IRF5) expression in human ductal carcinoma correlates with disease stage and contributes to metastasis. Breast Cancer Res. 2011; 13:R111.
149. Morelli E, Leone E, Cantafio ME, Di Martino MT, Amodio N, Biamonte L, Gulla A, Foresta U, Pitari MR, Botta C, Rossi M, Neri A, Munshi NC, Anderson KC, Tagliaferri P and Tassone P. Selective targeting of IRF4 by synthetic microRNA-125b-5p mimics induces anti-multiple myeloma activity in vitro and in vivo. Leukemia. 2015; 29:2173-2183.
150. Liu FC, Huang HS, Huang CY, Yang R, Chang DM, Lai JH and Ho LJ. A benzamide-linked small molecule HS-Cf inhibits TNF-alpha-induced interferon regulatory factor-1 in porcine chondrocytes: a potential disease-modifying drug for osteoarthritis therapeutics. J Clin Immunol. 2011; 31:1131-1142.
151. Zhao W, Qi J, Wang L, Zhang M, Wang P and Gao C. LY294002 inhibits TLR3/4-mediated IFN-beta production via inhibition of IRF3 activation with a PI3K-independent mechanism. FEBS Lett. 2012; 586:705-710.
152. Zhang X, Tao Y, Troiani L and Markovic-Plese S. Simvastatin inhibits IFN regulatory factor 4 expression and Th17 cell differentiation in CD4+ T cells derived from patients with multiple sclerosis. Journal of immunology. 2011; 187:3431-3437.
153. Dang O, Navarro L and David M. Inhibition of lipopolysaccharide-induced interferon regulatory factor 3 activation and protection from septic shock by hydroxystilbenes. Shock. 2004; 21:470-475.
154. Genin P, Morin P and Civas A. Impairment of interferoninduced IRF-7 gene expression due to inhibition of ISGF3 formation by trichostatin A. J Virol. 2003; 77:7113-7119.
155. Nikodemova M, Watters JJ, Jackson SJ, Yang SK and Duncan ID. Minocycline down-regulates MHC II expression in microglia and macrophages through inhibition of IRF-1 and protein kinase C (PKC)alpha/betaII. The Journal of biological chemistry. 2007; 282:15208-15216.
156. Furui J, Uegaki K, Yamazaki T, Shirakawa M, Swindells MB, Harada H, Taniguchi T and Kyogoku Y. Solution structure of the IRF-2 DNA-binding domain: a novel subgroup of the winged helix-turn-helix family. Structure. 1998; 6:491-500.
157. Fujii Y, Shimizu T, Kusumoto M, Kyogoku Y, Taniguchi T and Hakoshima T. Crystal structure of an IRF-DNA complex reveals novel DNA recognition and cooperative binding to a tandem repeat of core sequences. Embo Journal. 1999; 18:5028-5041.
158. Zhang HP, Kurosaki C, Yoshida M, Hayashi F and Yokoyama S. Solution structure of the IRF domain of human interferon regulator factors 4. Protein Data Bank. 2006.
159. Escalante CR, Nistal-Villan E, Shen LY, Garcia-Sastre A and Aggarwal AK. Structure of IRF-3 bound to the PRDIII-I regulatory element of the human interferon-beta enhancer. Mol Cell. 2007; 26:703-716.
160. Sali A and Blundell TL. Comparative protein modelling by satisfaction of spatial restraints. Journal of molecular biology. 1993; 234:779-815.
161. Dominguez C, Boelens R and Bonvin AM. HADDOCK: a protein-protein docking approach based on biochemical or biophysical information. J Am Chem Soc. 2003; 125:1731-1737.
162. Czerwoniec A, Szelag M, Juszczak K, Wesoly J and Bluyssen H. CAVS-Novel in silico selection strategy of specific STAT inhibitory compounds. J Comp Science. 2014.
163. Harrison C, Kiladjian JJ, Al-Ali HK, Gisslinger H, Waltzman R, Stalbovskaya V, McQuitty M, Hunter DS, Levy R, Knoops L, Cervantes F, Vannucchi AM, Barbui T and Barosi G. JAK inhibition with ruxolitinib versus best available therapy for myelofibrosis. N Engl J Med. 2012; 366:787-798.
164. Papp KA, Menter A, Strober B, Langley RG, Buonanno M, Wolk R, Gupta P, Krishnaswami S, Tan H and Harness JA. Efficacy and safety of tofacitinib, an oral Janus kinase inhibitor, in the treatment of psoriasis: a Phase 2b randomized placebo-controlled dose-ranging study. Br J Dermatol. 2012; 167:668-677.
165. Sandborn WJ, Ghosh S, Panes J, Vranic I, Su C, Rousell S, Niezychowski W and Study AI. Tofacitinib, an oral Janus kinase inhibitor, in active ulcerative colitis. N Engl J Med. 2012; 367:616-624.
166. Lee EB, Fleischmann R, Hall S, Wilkinson B, Bradley JD, Gruben D, Koncz T, Krishnaswami S, Wallenstein GV, Zang C, Zwillich SH, van Vollenhoven RF and Investigators OS. Tofacitinib versus methotrexate in rheumatoid arthritis. N Engl J Med. 2014; 370:2377-2386.
167. Wollenhaupt J, Silverfield J, Lee EB, Curtis JR, Wood SP, Soma K, Nduaka CI, Benda B, Gruben D, Nakamura H, Komuro Y, Zwillich SH, Wang L and Riese RJ. Safety and efficacy of tofacitinib, an oral janus kinase inhibitor, for the treatment of rheumatoid arthritis in open-label, longterm extension studies. J Rheumatol. 2014; 41:837-852.
168. Horiuchi M, Cui TX, Li Z, Li JM, Nakagami H and Iwai M. Fluvastatin enhances the inhibitory effects of a selective angiotensin II type 1 receptor blocker, valsartan, on vascular neointimal formation. Circulation. 2003; 107:106-112.
169. Banes-Berceli AK, Ketsawatsomkron P, Ogbi S, Patel B, Pollock DM and Marrero MB. Angiotensin II and endothelin-1 augment the vascular complications of diabetes via JAK2 activation. American journal of physiology Heart and circulatory physiology. 2007; 293:H1291-1299.
170. Wincewicz A, Sulkowska M, Rutkowski R, Sulkowski S, Musiatowicz B, Hirnle T, Famulski W, Koda M, Sokol G and Szarejko P. STAT1 and STAT3 as intracellular regulators of vascular remodeling. European Journal of Internal Medicine. 2007; 18:267-271.
171. Jiao S, Zheng X, Yang X, Zhang J and Wang L. Losartan inhibits STAT1 activation and protects human glomerular mesangial cells from angiotensin II induced premature senescence. Canadian journal of physiology and pharmacology. 2012; 90:89-98.
172. Jiao S, Meng F, Zhang J, Yang X, Zheng X and Wang L. STAT1 mediates cellular senescence induced by angiotensin II and H(2)O(2) in human glomerular mesangial cells. Molecular and cellular biochemistry. 2012; 365:9-17.
173. Tu SP, Jin H, Shi JD, Zhu LM, Suo Y, Lu G, Liu A, Wang TC and Yang CS. Curcumin induces the differentiation of myeloid-derived suppressor cells and inhibits their interaction with cancer cells and related tumor growth. Cancer prevention research. 2012; 5:205-215.
174. Dong Y, Lu B, Zhang X, Zhang J, Lai L, Li D, Wu Y, Song Y, Luo J, Pang X, Yi Z and Liu M. Cucurbitacin E, a tetracyclic triterpenes compound from Chinese medicine, inhibits tumor angiogenesis through VEGFR2-mediated Jak2-STAT3 signaling pathway. Carcinogenesis. 2010; 31:2097-2104.
175. Sun J, Blaskovich MA, Jove R, Livingston SK, Coppola D and Sebti SM. Cucurbitacin Q: a selective STAT3 activation inhibitor with potent antitumor activity. Oncogene. 2005; 24:3236-3245.
176. Fossey SL, Bear MD, Lin J, Li C, Schwartz EB, Li PK, Fuchs JR, Fenger J, Kisseberth WC and London CA. The novel curcumin analog FLLL32 decreases STAT3 DNA binding activity and expression, and induces apoptosis in osteosarcoma cell lines. BMC cancer. 2011; 11:112.
177. Onimoe GI, Liu A, Lin L, Wei CC, Schwartz EB, Bhasin D, Li C, Fuchs JR, Li PK, Houghton P, Termuhlen A, Gross T and Lin J. Small molecules, LLL12 and FLLL32, inhibit STAT3 and exhibit potent growth suppressive activity in osteosarcoma cells and tumor growth in mice. Investigational new drugs. 2012; 30:916-926.
178. Li T, Wang W, Chen H, Li T and Ye L. Evaluation of anti-leukemia effect of resveratrol by modulating STAT3 signaling. International immunopharmacology. 2010; 10:18-25.
179. Shinriki S, Jono H, Ota K, Ueda M, Kudo M, Ota T, Oike Y, Endo M, Ibusuki M, Hiraki A, Nakayama H, Yoshitake Y, Shinohara M and Ando Y. Humanized anti-interleukin-6 receptor antibody suppresses tumor angiogenesis and in vivo growth of human oral squamous cell carcinoma. Clin Cancer Res. 2009; 15:5426-5434.
180. Zgheib A, Pelletier-Bonnier E, Levros LC, Jr. and Annabi B. Selective JAK/STAT3 signalling regulates transcription of colony stimulating factor-2 and-3 in Concanavalin-A-activated mesenchymal stromal cells. Cytokine. 2013; 63:187-193.
181. Xin H, Herrmann A, Reckamp K, Zhang W, Pal S, Hedvat M, Zhang C, Liang W, Scuto A, Weng S, Morosini D, Cao ZA, Zinda M, Figlin R, Huszar D, Jove R, et al. Antiangiogenic and antimetastatic activity of JAK inhibitor AZD1480. Cancer research. 2011; 71:6601-6610.
182. Pardanani A, Tefferi A, Jamieson C, Gabrail NY, Lebedinsky C, Gao G, Liu F, Xu C, Cao H and Talpaz M. A phase 2 randomized dose-ranging study of the JAK2-selective inhibitor fedratinib (SAR302503) in patients with myelofibrosis. Blood Cancer J. 2015; 5:e335.
183. Klein JD, Sano D, Sen M, Myers JN, Grandis JR and Kim S. STAT3 oligonucleotide inhibits tumor angiogenesis in preclinical models of squamous cell carcinoma. PloS one. 2014; 9:e81819.
184. Daniel JM, Dutzmann J, Bielenberg W, Widmer-Teske R, Gunduz D, Hamm CW and Sedding DG. Inhibition of STAT3 signaling prevents vascular smooth muscle cell proliferation and neointima formation. Basic Res Cardiol. 2012; 107:261.
185. Gurbuz V, Konac E, Varol N, Yilmaz A, Gurocak S, Menevse S and Sozen S. Effects of AG490 and S3I-201 on regulation of the JAK/STAT3 signaling pathway in relation to angiogenesis in TRAIL-resistant prostate cancer cells. Oncol Lett. 2014; 7:755-763.
186. Unni S, Huang Y, Hanson RM, Tobias M, Krishnan S, Li WW, Nielsen JE and Baker NA. Web servers and services for electrostatics calculations with APBS and PDB2PQR. Journal of computational chemistry. 2011; 32:1488-1491.
187. Jain AN. Surflex: fully automatic flexible molecular docking using a molecular similarity-based search engine. Journal of medicinal chemistry. 2003; 46:499-511.
188. Kurowski MA and Bujnicki JM. GeneSilico protein structure prediction meta-server. Nucleic acids research. 2003; 31:3305-3307.
189. Rice P, Longden I and Bleasby A. EMBOSS: the European Molecular Biology Open Software Suite. Trends Genet. 2000; 16:276-277.
190. van Dijk M and Bonvin AM. 3D-DART: a DNA structure modelling server. Nucleic acids research. 2009; 37:W235-239.