STAT1 and IRF8 in Vascular Inflammation and Cardiovascular Disease: Diagnostic and Therapeutic Potential

International Reviews of Immunology

Volumn 35, Issue 5, 2016, Pages 434-454

  Chmielewski, Stefan ^a,b   Piaszyk Borychowska, Anna ^a   Wesoly, Joanna ^a   Bluyssen, Hans A R ^a  

^a ADAM MICKIEWICZ UNIVERSITY   (Poland)

^b TECHNICAL UNIVERSITY OF MUNICH   (Germany)

Author keywords

atherosclerosis; diagnostic marker; IFN ; IRF8; signal integration; STAT1; therapeutic target; TLR4

Indexed keywords

ANTIINFLAMMATORY AGENT; BIOLOGICAL MARKER; GAMMA INTERFERON; IMMUNOSUPPRESSIVE AGENT; INTERFERON CONSENSUS SEQUENCE BINDING PROTEIN; STAT1 PROTEIN; TOLL LIKE RECEPTOR 4; INTERFERON REGULATORY FACTOR;

ATHEROSCLEROSIS; CARDIOVASCULAR DISEASE; CELL FUNCTION; CHRONIC INFLAMMATION; DIAGNOSTIC VALUE; DRUG TARGETING; GENE TARGETING; HUMAN; IMMUNOCOMPETENT CELL; MOLECULAR INTERACTION; PRIORITY JOURNAL; REVIEW; SIGNAL TRANSDUCTION; VASCULITIS; ANIMAL; ENDOTHELIUM CELL; IMMUNOLOGY; IMMUNOSUPPRESSIVE TREATMENT; INFLAMMATION; METABOLISM; SMOOTH MUSCLE CELL;

ANIMALS; CARDIOVASCULAR DISEASES; ENDOTHELIAL CELLS; HUMANS; IMMUNOSUPPRESSION; INFLAMMATION; INTERFERON REGULATORY FACTORS; MYOCYTES, SMOOTH MUSCLE; STAT1 TRANSCRIPTION FACTOR; VASCULITIS;

EID: 84947920360     PISSN: 08830185     EISSN: 15635244     Source Type: Journal    
DOI: 10.3109/08830185.2015.1087519     Document Type: Review

References (125)

1. Mathers CD, Loncar D. Projections of global mortality and burden of disease from 2002 to 2030. PLoS Med. 2006;3(11):e442. Epub 2006/11/30. doi:06-PLME-RA-0071R2 [pii] 10.1371/journal.pmed.0030442. PubMed PMID:17132052; PubMed Central PMCID:PMC1664601.
2. Hansson GK, Hermansson A. The immune system in atherosclerosis. Nat Immunol. 2011;12(3):204–212. Epub 2011/02/16. doi:10.1038/ni.2001 ni.2001 [pii]. PubMed PMID:21321594.
3. Stark GR, Darnell JE, Jr. The JAK-STAT pathway at twenty. Immunity. 2012;36(4):503–514. Epub 2012/04/24. doi:10.1016/j.immuni.2012.03.013 S1074-7613(12)00132-X [pii]. PubMed PMID:22520844; PubMed Central PMCID:PMC3909993.
4. Pitha PM, SpringerLink (Online service). Interferon:The 50th Anniversary. Berlin, Heidelberg:Springer-Verlag, 2007. Available from:http://dx.doi.org/10.1007/978-3-540-71329-6.
5. Wesoly J, Szweykowska-Kulinska Z, Bluyssen HA. STAT activation and differential complex formation dictate selectivity of interferon responses. Acta Biochim Pol. 2007;54(1):27–38. Epub 2007/03/14. doi:20071423 [pii]. PubMed PMID:17351669.
6. Schindler C, Plumlee C. Inteferons pen the JAK-STAT pathway. Semin Cell Dev Biol. 2008;19(4):311–318. Epub 2008/09/04. doi:10.1016/j.semcdb.2008.08.010 S1084-9521(08)00070-0 [pii]. PubMed PMID:18765289; PubMed Central PMCID:PMC2741134.
7. Tamura T, Yanai H, Savitsky D, Taniguchi T. The IRF family transcription factors in immunity and oncogenesis. Annu Rev Immunol. 2008;26:535–584. Epub 2008/02/29. doi:10.1146/annurev.immunol.26.021607.090400. PubMed PMID:18303999.
8. Lu Z, Zhang X, Li Y, Jin J, Huang Y. TLR4 antagonist reduces early-stage atherosclerosis in diabetic apolipoprotein E-deficient mice. J Endocrinol. 2013;216(1):61–71. doi:10.1530/JOE-12-0338. PubMed PMID:23060524.
9. Ross R. Atherosclerosis–an inflammatory disease. N Engl J Med. 1999;340(2):115–126. Epub 1999/01/14. doi:10.1056/NEJM199901143400207. PubMed PMID:9887164.
10. Hansson GK, Libby P. The immune response in atherosclerosis:a double-edged sword. Nat Rev Immunol. 2006;6(7):508–519. Epub 2006/06/17. doi:nri1882 [pii] 10.1038/nri1882. PubMed PMID:16778830.
11. Davignon J, Ganz P. Role of endothelial dysfunction in atherosclerosis. Circulation. 2004;109(23 Suppl 1):III27–32. Epub 2004/06/17. doi:10.1161/01.CIR.0000131515.03336.f8 109/23_suppl_1/III-27 [pii]. PubMed PMID:15198963.
12. Cole JE, Georgiou E, Monaco C. The expression and functions of toll-like receptors in atherosclerosis. Mediators Inflamm. 2010;2010:393946. doi:10.1155/2010/393946. PubMed PMID:20652007; PubMed Central PMCID:PMC2905957.
13. Combadiere C, Potteaux S, Rodero M, Combined inhibition of CCL2, CX3CR1, and CCR5 abrogates Ly6C(hi) and Ly6C(lo) monocytosis and almost abolishes atherosclerosis in hypercholesterolemic mice. Circulation. 2008;117(13):1649–1657. Epub 2008/03/19. doi:10.1161/CIRCULATIONAHA.107.745091 CIRCULATIONAHA.107.745091 [pii]. PubMed PMID:18347211.
14. Moore KJ, Sheedy FJ, Fisher EA. Macrophages in atherosclerosis:a dynamic balance. Nat Rev Immunol. 2013;1310:709–721. Epub 2013/09/03. doi:10.1038/nri3520 nri3520 [pii]. PubMed PMID:23995626.
15. Tacke F, Alvarez D, Kaplan TJ, Monocyte subsets differentially employ CCR2, CCR5, and CX3CR1 to accumulate within atherosclerotic plaques. J Clin Invest. 2007;117(1):185–194. Epub 2007/01/04. doi:10.1172/JCI28549. PubMed PMID:17200718; PubMed Central PMCID:PMC1716202.
16. Smith JD, Trogan E, Ginsberg M, Decreased atherosclerosis in mice deficient in both macrophage colony-stimulating factor (op) and apolipoprotein E. Proc Natl Acad Sci U S A. 1995;92(18):8264–8268. Epub 1995/08/29. PubMed PMID:7667279; PubMed Central PMCID:PMC41137.
17. Allahverdian S, Chehroudi AC, McManus BM, Contribution of intimal smooth muscle cells to cholesterol accumulation and macrophage-like cells in human atherosclerosis. Circulation. 2014;129(15):1551–1559. Epub 2014/02/01. doi:10.1161/CIRCULATIONAHA.113.005015 CIRCULATIONAHA.113.005015 [pii]. PubMed PMID:24481950.
18. Adamson S, Leitinger N. Phenotypic modulation of macrophages in response to plaque lipids. Curr Opin Lipidol. 2011;22(5):335–342. Epub 2011/08/16. doi:10.1097/MOL.0b013e32834a97e4. PubMed PMID:21841486; PubMed Central PMCID:PMC3979355.
19. Fredman G, Spite M. Recent advances in the role of immunity in atherosclerosis. Circ Res. 2013;113(12):e111–e114. Epub 2013/12/07. doi:10.1161/CIRCRESAHA.113.302986 CIRCRESAHA.113.302986 [pii]. PubMed PMID:24311619.
20. Packard RR, Maganto-Garcia E, Gotsman I, CD11c(+) dendritic cells maintain antigen processing, presentation capabilities, and CD4(+) T-cell priming efficacy under hypercholesterolemic conditions associated with atherosclerosis. Circ Res. 2008;103(9):965–973. Epub 2008/10/04. doi:10.1161/CIRCRESAHA.108.185793 CIRCRESAHA.108.185793 [pii]. PubMed PMID:18832748; PubMed Central PMCID:PMC2668806.
21. Witztum JL, Lichtman AH. The influence of innate and adaptive immune responses on atherosclerosis. Annu Rev Pathol. 2014;9:73–102. Epub 2013/08/14. doi:10.1146/annurev-pathol-020712-163936. PubMed PMID:23937439; PubMed Central PMCID:PMC3988528.
22. Sancho D, Joffre OP, Keller AM, et al. Identification of a dendritic cell receptor that couples sensing of necrosis to immunity. Nature. 2009;458(7240):899–903. doi:10.1038/nature07750. PubMed PMID:19219027; PubMed Central PMCID:PMC2671489.
23. Jonasson L, Holm J, Skalli O, Regional accumulations of T cells, macrophages, and smooth muscle cells in the human atherosclerotic plaque. Arteriosclerosis. 1986;6(2):131–138. Epub 1986/03/01. PubMed PMID:2937395.
24. Mallat Z, Taleb S, Ait-Oufella H, Tedgui A. The role of adaptive T cell immunity in atherosclerosis. J Lipid Res. 2009;50 Suppl:S364—S39. Epub 2008/12/04. doi:10.1194/jlr.R800092-JLR200 R800092-JLR200 [pii]. PubMed PMID:19050311; PubMed Central PMCID:PMC2674704.
25. Buono C, Binder CJ, Stavrakis G, T-bet deficiency reduces atherosclerosis and alters plaque antigen-specific immune responses. Proc Natl Acad Sci USA. 2005;102(5):1596–1601. Epub 2005/01/25. doi:0409015102 [pii] 10.1073/pnas.0409015102. PubMed PMID:15665085; PubMed Central PMCID:PMC547865.
26. Medzhitov R. Toll-like receptors and innate immunity. Nat Rev Immunol. 2001;1(2):135–145. Epub 2002/03/22. doi:10.1038/35100529. PubMed PMID:11905821.
27. Kawai T, Akira S. The role of pattern-recognition receptors in innate immunity:update on Toll-like receptors. Nat Immunol. 2010;11(5):373–384. Epub 2010/04/21. doi:10.1038/ni.1863 ni.1863 [pii]. PubMed PMID:20404851.
28. Cani PD, Amar J, Iglesias MA, et al. Metabolic endotoxemia initiates obesity and insulin resistance. Diabetes. 2007;56(7):1761–1772. doi:10.2337/db06-1491. PubMed PMID:17456850.
29. Amar J, Burcelin R, Ruidavets JB, et al. Energy intake is associated with endotoxemia in apparently healthy men. Am J Clin Nutr. 2008;87(5):1219–23. PubMed PMID:18469242.
30. Szeto CC, Kwan BC, Chow KM, et al. Endotoxemia is related to systemic inflammation and atherosclerosis in peritoneal dialysis patients. Clin J Am Soc Nephrol. 2008;3(2):431–436. doi:10.2215/CJN.03600807. PubMed PMID:18256376; PubMed Central PMCID:PMC2390956.
31. Laugerette F, Vors C, Peretti N, Michalski MC. Complex links between dietary lipids, endogenous endotoxins and metabolic inflammation. Biochimie. 2011;93(1):39–45. doi:10.1016/j.biochi.2010.04.016. PubMed PMID:20433893.
32. Kanellakis P, Agrotis A, Kyaw TS, et al. High-mobility group box protein 1 neutralization reduces development of diet-induced atherosclerosis in apolipoprotein e-deficient mice. Arterioscler Thromb Vasc Biol. 2011;31(2):313–319. doi:10.1161/ATVBAHA.110.218669. PubMed PMID:21088249.
33. Erridge C. The roles of Toll-like receptors in atherosclerosis. J Innate Immun. 2009;1(4):340–349. doi:10.1159/000191413. PubMed PMID:20375591.
34. Methe H, Zimmer E, Grimm C, Evidence for a role of toll-like receptor 4 in development of chronic allograft rejection after cardiac transplantation. Transplantation. 2004;78(9):1324–1331. PubMed PMID:15548971.
35. Higashimori M, Tatro JB, Moore KJ, Role of toll-like receptor 4 in intimal foam cell accumulation in apolipoprotein E-deficient mice. Arterioscler Thromb Vasc Biol. 2011;31(1):50–57. Epub 2010/10/23. doi:10.1161/ATVBAHA.110.210971 ATVBAHA.110.210971 [pii]. PubMed PMID:20966403; PubMed Central PMCID:PMC3034636.
36. Methe H, Kim JO, Kofler S, Expansion of circulating Toll-like receptor 4-positive monocytes in patients with acute coronary syndrome. Circulation. 2005;111(20):2654–2661. Epub 2005/05/11. doi:CIRCULATIONAHA.104.498865 [pii] 10.1161/CIRCULATIONAHA.104.498865. PubMed PMID:15883205.
37. Michelsen KS, Wong MH, Shah PK, Lack of Toll-like receptor 4 or myeloid differentiation factor 88 reduces atherosclerosis and alters plaque phenotype in mice deficient in apolipoprotein E. Proc Natl Acad Sci USA. 2004;101(29):10679–10684. Epub 2004/07/14. doi:10.1073/pnas.0403249101 0403249101 [pii]. PubMed PMID:15249654; PubMed Central PMCID:PMC489994.
38. Timmers L, Sluijter JP, van Keulen JK, et al. Toll-like receptor 4 mediates maladaptive left ventricular remodeling and impairs cardiac function after myocardial infarction. Circ Res. 2008;102(2):257–264. doi:10.1161/CIRCRESAHA.107.158220. PubMed PMID:18007026.
39. Sollinger D, Eissler R, Lorenz S, et al. Damage-associated molecular pattern activated Toll-like receptor 4 signalling modulates blood pressure in L-NAME-induced hypertension. Cardiovasc Res. 2014;101(3):464–472. Epub 2013/12/05. doi:10.1093/cvr/cvt265 cvt265 [pii]. PubMed PMID:24302630.
40. Harrison DG, Guzik TJ, Lob HE, et al. Inflammation, immunity, and hypertension. Hypertension. 2011;57(2):132–140. Epub 2010/12/15. doi:HYPERTENSIONAHA.110.163576 [pii] 10.1161/HYPERTENSIONAHA.110.163576. PubMed PMID:21149826; PubMed Central PMCID:PMC3028593.
41. Stasch JP, Becker EM, Alonso-Alija C, NO-independent regulatory site on soluble guanylate cyclase. Nature. 2001;410(6825):212–215. Epub 2001/03/10. doi:10.1038/35065611 35065611 [pii]. PubMed PMID:11242081.
42. Gupta S, Pablo AM, Jiang X, IFN-gamma potentiates atherosclerosis in ApoE knock-out mice. J Clin Invest. 1997;99(11):2752–2761. Epub 1997/06/01. doi:10.1172/JCI119465. PubMed PMID:9169506; PubMed Central PMCID:PMC508122.
43. Nagano H, Mitchell RN, Taylor MK, Interferon-gamma deficiency prevents coronary arteriosclerosis but not myocardial rejection in transplanted mouse hearts. J Clin Invest. 1997;100(3):550–557. Epub 1997/08/01. doi:10.1172/JCI119564. PubMed PMID:9239401; PubMed Central PMCID:PMC508221.
44. Raisanen-Sokolowski A, Glysing-Jensen T, Koglin J, Russell ME. Reduced transplant arteriosclerosis in murine cardiac allografts placed in interferon-gamma knockout recipients. Am J Pathol. 1998;152(2):359–365. Epub 1998/02/18. PubMed PMID:9466561; PubMed Central PMCID:PMC1857959.
45. Nagano H, Libby P, Taylor MK, et al. Coronary arteriosclerosis after T-cell-mediated injury in transplanted mouse hearts:role of interferon-gamma. Am J Pathol. 1998;152(5):1187–1197. Epub 1998/05/20. PubMed PMID:9588888; PubMed Central PMCID:PMC1858591.
46. Whitman SC, Ravisankar P, Elam H, Daugherty A. Exogenous interferon-gamma enhances atherosclerosis in apolipoprotein E−/− mice. Am J Pathol. 2000;157(6):1819–1824. Epub 2000/12/07. doi:S0002-9440(10)64820-1 [pii]. PubMed PMID:11106554; PubMed Central PMCID:PMC1885762.
47. Russell PS, Chase CM, Winn HJ, Colvin RB. Coronary atherosclerosis in transplanted mouse hearts. III. Effects of recipient treatment with a monoclonal antibody to interferon-gamma. Transplantation. 1994;57(9):1367–1371. Epub 1994/05/15. PubMed PMID:7910422.
48. Tellides G, Tereb DA, Kirkiles-Smith NC, et al. Interferon-gamma elicits arteriosclerosis in the absence of leukocytes. Nature. 2000;403(6766):207–211. Epub 2000/01/26. doi:10.1038/35003221. PubMed PMID:10646607.
49. Rocha VZ, Folco EJ, Sukhova G, et al. Interferon-gamma, a Th1 cytokine, regulates fat inflammation:a role for adaptive immunity in obesity. Circ Res. 2008;103(5):467–476. Epub 2008/07/29. doi:10.1161/CIRCRESAHA.108.177105 CIRCRESAHA.108.177105 [pii]. PubMed PMID:18658050; PubMed Central PMCID:PMC2740384.
50. Mao X, Ren Z, Parker GN, Structural bases of unphosphorylated STAT1 association and receptor binding. Mol Cell. 2005;17(6):761–771. Epub 2005/03/23. doi:S1097-2765(05)01120-2 [pii] 10.1016/j.molcel.2005.02.021. PubMed PMID:15780933.
51. Braunstein J, Brutsaert S, Olson R, Schindler C. STATs dimerize in the absence of phosphorylation. J Biol Chem. 2003;278(36):34133–34140. Epub 2003/07/02. doi:10.1074/jbc.M304531200 M304531200 [pii]. PubMed PMID:12832402.
52. Liu L, Okada S, Kong XF, Gain-of-function human STAT1 mutations impair IL-17 immunity and underlie chronic mucocutaneous candidiasis. J Exp Med. 2011;208(8):1635–1648. Epub 2011/07/06. doi:10.1084/jem.20110958 jem.20110958 [pii]. PubMed PMID:21727188; PubMed Central PMCID:PMC3149226.
53. Kiu H, Nicholson SE. Biology and significance of the JAK/STAT signalling pathways. Growth Factors. 2012;30(2):88–106. Epub 2012/02/22. doi:10.3109/08977194.2012.660936. PubMed PMID:22339650; PubMed Central PMCID:PMC3762697.
54. Mertens C, Zhong M, Krishnaraj R, Dephosphorylation of phosphotyrosine on STAT1 dimers requires extensive spatial reorientation of the monomers facilitated by the N-terminal domain. Genes Dev. 2006;20(24):3372–3381. Epub 2006/12/22. doi:20/24/3372 [pii] 10.1101/gad.1485406. PubMed PMID:17182865; PubMed Central PMCID:PMC1698445.
55. Zhong M, Henriksen MA, Takeuchi K, et al. Implications of an antiparallel dimeric structure of nonphosphorylated STAT1 for the activation-inactivation cycle. Proc Natl Acad Sci U S A. 2005;102(11):3966–3971. Epub 2005/03/09. doi:0501063102 [pii] 10.1073/pnas.0501063102. PubMed PMID:15753310; PubMed Central PMCID:PMC554839.
56. Platanias LC. Mechanisms of type-I- and type-II-interferon-mediated signalling. Nat Rev Immunol. 2005;5(5):375–386. Epub 2005/05/03. doi:nri1604 [pii] 10.1038/nri1604. PubMed PMID:15864272.
57. Levy DE, Darnell JE, Jr. Stats:transcriptional control and biological impact. Nat Rev Mol Cell Biol. 2002;3(9):651–662. Epub 2002/09/05. doi:10.1038/nrm909 nrm909 [pii]. PubMed PMID:12209125.
58. Wen Z, Zhong Z, Darnell JE, Jr. Maximal activation of transcription by Stat1 and Stat3 requires both tyrosine and serine phosphorylation. Cell. 1995;82(2):241–250. Epub 1995/07/28. doi:0092-8674(95)90311-9 [pii]. PubMed PMID:7543024.
59. Wen Z, Darnell JE, Jr. Mapping of Stat3 serine phosphorylation to a single residue (727) and evidence that serine phosphorylation has no influence on DNA binding of Stat1 and Stat3. Nucleic Acids Res. 1997;25(11):2062–2067. Epub 1997/06/01. doi:gka365 [pii]. PubMed PMID:9153303; PubMed Central PMCID:PMC146718.
60. Zhuang S. Regulation of STAT signaling by acetylation. Cell Signal. 2013;25(9):1924–1931. Epub 2013/05/28. doi:10.1016/j.cellsig.2013.05.007 S0898-6568(13)00132-0 [pii]. PubMed PMID:23707527.
61. Icardi L, De Bosscher K, Tavernier J. The HAT/HDAC interplay:multilevel control of STAT signaling. Cytokine Growth Factor Rev. 2012;23(6):283–291. Epub 2012/09/20. doi:10.1016/j.cytogfr.2012.08.002 S1359-6101(12)00066-4 [pii]. PubMed PMID:22989617.
62. Kramer OH, Heinzel T. Phosphorylation-acetylation switch in the regulation of STAT1 signaling. Mol Cell Endocrinol. 2010;315(1–2):40–48. Epub 2009/11/03. doi:10.1016/j.mce.2009.10.007 S0303-7207(09)00551-6 [pii]. PubMed PMID:19879327.
63. Antunes F, Marg A, Vinkemeier U. STAT1 signaling is not regulated by a phosphorylation-acetylation switch. Mol Cell Biol. 2011;31(14):3029-3037. Epub 2011/05/18. doi:10.1128/MCB.05300-11 MCB.05300-11 [pii]. PubMed PMID:21576370; PubMed Central PMCID:PMC3133404.
64. Begitt A, Droescher M, Knobeloch KP, Vinkemeier U. SUMO conjugation of STAT1 protects cells from hyperresponsiveness to IFNgamma. Blood. 2011;118(4):1002–1007. Epub 2011/06/04. doi:10.1182/blood-2011-04-347930 blood-2011-04-347930 [pii]. PubMed PMID:21636857.
65. Hertzog PJ, O’Neill LA, Hamilton JA. The interferon in TLR signaling:more than just antiviral. Trends Immunol. 2003;24(10):534–539. PubMed PMID:14552837.
66. Decker T, Muller M, Stockinger S. The yin and yang of type I interferon activity in bacterial infection. Nat Rev Immunol. 2005;5(9):675–687. doi:10.1038/nri1684. PubMed PMID:16110316.
67. O’Neill LA, Bowie AG. The family of five:TIR-domain-containing adaptors in Toll-like receptor signalling. Nat Rev Immunol. 2007;7(5):353–364. doi:10.1038/nri2079. PubMed PMID:17457343.
68. Sikorski K, Chmielewski S, Olejnik A, STAT1 as a central mediator of IFNgamma and TLR4 signal integration in vascular dysfunction. JAKSTAT. 2012;1(4):241–249. Epub 2013/09/24. doi:10.4161/jkst.22469 2012JAKS0052R [pii]. PubMed PMID:24058779; PubMed Central PMCID:PMC3670280.
69. Chmielewski S, Olejnik A, Sikorski K, Pelisek J, Blaszczyk K, Aoqui C, STAT1-Dependent Signal Integration between IFNgamma and TLR4 in Vascular Cells Reflect Pro-Atherogenic Responses in Human Atherosclerosis. PLoS One. 2014;9(12):e113318. Epub 2014/12/06. doi:10.1371/journal.pone.0113318 PONE-D-14-17335 [pii]. PubMed PMID:25478796.
70. Sikorski K, Chmielewski S, Przybyl L, STAT1-mediated signal integration between IFNgamma and LPS leads to increased EC and SMC activation and monocyte adhesion. Am J Physiol Cell Physiol. 2011;300(6):C1337—C144. Epub 2011/02/25. doi:ajpcell.00276.2010 [pii] 10.1152/ajpcell.00276.2010. PubMed PMID:21346151.
71. Schiavoni G, Mattei F, Sestili P, ICSBP is essential for the development of mouse type I interferon-producing cells and for the generation and activation of CD8alpha(+) dendritic cells. J Exp Med. 2002;196(11):1415–1425. PubMed PMID:12461077; PubMed Central PMCID:PMC2194263.
72. Tsujimura H, Tamura T, Ozato K. Cutting edge:IFN consensus sequence binding protein/IFN regulatory factor 8 drives the development of type I IFN-producing plasmacytoid dendritic cells. Journal of immunology. 2003;170(3):1131–1135. PubMed PMID:12538667.
73. Tsujimura H, Tamura T, Kong HJ, Toll-like receptor 9 signaling activates NF-kappaB through IFN regulatory factor-8/IFN consensus sequence binding protein in dendritic cells. J Immunol. 2004;172(11):6820–6827. Epub 2004/05/22. PubMed PMID:15153500.
74. Zhao J, Kong HJ, Li H, IRF-8/interferon (IFN) consensus sequence-binding protein is involved in Toll-like receptor (TLR) signaling and contributes to the cross-talk between TLR and IFN-gamma signaling pathways. J Biol Chem. 2006;281(15):10073–10080. Epub 2006/02/18. doi:M507788200 [pii] 10.1074/jbc.M507788200. PubMed PMID:16484229.
75. Escalante CR, Brass AL, Pongubala JM, Crystal structure of PU.1/IRF-4/DNA ternary complex. Mol Cell. 2002;10(5):1097–1105. PubMed PMID:12453417.
76. Glasmacher E, Agrawal S, Chang AB, A genomic regulatory element that directs assembly and function of immune-specific AP-1-IRF complexes. Science. 2012;338(6109):975–980. doi:10.1126/science.1228309. PubMed PMID:22983707.
77. Li P, Spolski R, Liao W, BATF-JUN is critical for IRF4-mediated transcription in T cells. Nature. 2012;490(7421):543–546. doi:10.1038/nature11530. PubMed PMID:22992523; PubMed Central PMCID:PMC3537508.
78. Tamura T, Thotakura P, Tanaka TS, Identification of target genes and a unique cis element regulated by IRF-8 in developing macrophages. Blood. 2005;106(6):1938–1947. doi:10.1182/blood-2005-01-0080. PubMed PMID:15947094; PubMed Central PMCID:PMC1895144.
79. Tussiwand R, Lee WL, Murphy TL, Compensatory dendritic cell development mediated by BATF-IRF interactions. Nature. 2012;490(7421):502–507. doi:10.1038/nature11531. PubMed PMID:22992524; PubMed Central PMCID:PMC3482832.
80. Unlu S, Kumar A, Waterman WR, Phosphorylation of IRF8 in a pre-associated complex with Spi-1/PU.1 and non-phosphorylated Stat1 is critical for LPS induction of the IL1B gene. Mol Immunol. 2007;44(13):3364–3379. doi:10.1016/j.molimm.2007.02.016. PubMed PMID:17386941; PubMed Central PMCID:PMC2719065.
81. Konieczna I, Horvath E, Wang H, Constitutive activation of SHP2 in mice cooperates with ICSBP deficiency to accelerate progression to acute myeloid leukemia. J Clin Invest. 2008;118(3):853–867. doi:10.1172/JCI33742. PubMed PMID:18246201; PubMed Central PMCID:PMC2214847.
82. Sharf R, Meraro D, Azriel A, Phosphorylation events modulate the ability of interferon consensus sequence binding protein to interact with interferon regulatory factors and to bind DNA. J Biol Chem. 1997;272(15):9785–9792. PubMed PMID:9092512.
83. Cohen H, Azriel A, Cohen T, 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. J Biol Chem. 2000;275(50):39081–39089. doi:10.1074/jbc.M004900200. PubMed PMID:10991940.
84. Kanno Y, Levi BZ, Tamura T, Ozato K. Immune cell-specific amplification of interferon signaling by the IRF-4/8-PU.1 complex. J Interferon Cytokine Res. 2005;25(12):770–779. Epub 2005/12/27. doi:10.1089/jir.2005.25.770. PubMed PMID:16375605.
85. Hu X, Chen J, Wang L, Ivashkiv LB. Crosstalk among Jak-STAT, Toll-like receptor, and ITAM-dependent pathways in macrophage activation. J Leukoc Biol. 2007;82(2):237–243. Epub 2007/05/16. doi:jlb.1206763 [pii] 10.1189/jlb.1206763. PubMed PMID:17502339.
86. Schroder K, Sweet MJ, Hume DA. Signal integration between IFNgamma and TLR signalling pathways in macrophages. Immunobiology. 2006;211(6–8):511–524. doi:10.1016/j.imbio.2006.05.007. PubMed PMID:16920490.
87. Hu X, Chakravarty SD, Ivashkiv LB. Regulation of interferon and Toll-like receptor signaling during macrophage activation by opposing feedforward and feedback inhibition mechanisms. Immunol Rev. 2008;226:41–56. Epub 2009/01/24. doi:10.1111/j.1600-065X.2008.00707.x IMR707 [pii]. PubMed PMID:19161415; PubMed Central PMCID:PMC2630590.
88. Hu X, Ivashkiv LB. Cross-regulation of signaling pathways by interferon-gamma:implications for immune responses and autoimmune diseases. Immunity. 2009;31(4):539–550. doi:10.1016/j.immuni.2009.09.002. PubMed PMID:19833085; PubMed Central PMCID:PMC2774226.
89. Mulvany MJ, Halpern W. Contractile properties of small arterial resistance vessels in spontaneously hypertensive and normotensive rats. Circ Res. 1977;41(1):19–26. PubMed PMID:862138.
90. Ades EW, Candal FJ, Swerlick RA, HMEC-1:establishment of an immortalized human microvascular endothelial cell line. J Invest Dermatol. 1992;99(6):683–690. Epub 1992/12/01. PubMed PMID:1361507.
91. Liu J, Ma X. Interferon regulatory factor 8 regulates RANTES gene transcription in cooperation with interferon regulatory factor-1, NF-kappaB, and PU.1. J Biol Chem. 2006;281(28):19188–19195. doi:10.1074/jbc.M602059200. PubMed PMID:16707500.
92. Agrawal S, Febbraio M, Podrez E, Signal transducer and activator of transcription 1 is required for optimal foam cell formation and atherosclerotic lesion development. Circulation. 2007;115(23):2939–2947. Epub 2007/05/30. doi:CIRCULATIONAHA.107.696922 [pii] 10.1161/CIRCULATIONAHA.107.696922. PubMed PMID:17533179.
93. Lim WS, Timmins JM, Seimon TA, 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(7):940–951. Epub 2008/01/30. doi:10.1161/CIRCULATIONAHA.107.711275 CIRCULATIONAHA.107.711275 [pii]. PubMed PMID:18227389; PubMed Central PMCID:PMC2276635.
94. Zhou XX, Gao PJ, 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(4):373–379. Epub 2008/11/21. doi:10.1111/j.1440-1681.2008.05067.x CEP5067 [pii]. PubMed PMID:19018808.
95. Stadlbauer TH, Wagner AH, Holschermann H, Fiedel S, Fingerhuth H, Tillmanns H, AP-1 and STAT-1 decoy oligodeoxynucleotides attenuate transplant vasculopathy in rat cardiac allografts. Cardiovasc Res. 2008;79(4):698–705. Epub 2008/05/31. doi:10.1093/cvr/cvn135 cvn135 [pii]. PubMed PMID:18511434.
96. Chung HK, Lee IK, Kang H, Statin inhibits interferon-gamma-induced expression of intercellular adhesion molecule-1 (ICAM-1) in vascular endothelial and smooth muscle cells. Exp Mol Med. 2002;34(6):451–461. Epub 2003/01/15. doi:200212318 [pii]. PubMed PMID:12526087.
97. Kirchmer MN, Franco A, Albasanz-Puig A, Modulation of vascular smooth muscle cell phenotype by STAT-1 and STAT-3. Atherosclerosis. 2014;234(1):169–175. doi:10.1016/j.atherosclerosis.2014.02.029. PubMed PMID:24657387.
98. Torella D, Curcio A, Gasparri C, Fludarabine prevents smooth muscle proliferation in vitro and neointimal hyperplasia in vivo through specific inhibition of STAT-1 activation. Am J Physiol Heart Circ Physiol. 2007;292(6):H2935–43. Epub 2007/02/13. doi:00887.2006 [pii] 10.1152/ajpheart.00887.2006. PubMed PMID:17293493.
99. Moll HP, Lee A, Minussi DC, da Silva CG, Csizmadia E, Bhasin M, A20 regulates atherogenic interferon (IFN)-gamma signaling in vascular cells by modulating basal IFNbeta levels. J Biol Chem. 2014;289(45):30912–30924. doi:10.1074/jbc.M114.591966. PubMed PMID:25217635; PubMed Central PMCID:PMC4223299.
100. Knight RA, Scarabelli TM, Stephanou A. STAT transcription in the ischemic heart. JAKSTAT. 2012;1(2):111–1117. Epub 2012/04/01. doi:10.4161/jkst.20078 2012JAKS0018R [pii]. PubMed PMID:24058759; PubMed Central PMCID:PMC3670290.
101. Manea A, Tanase LI, Raicu M, 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(1):105–112. doi:10.1161/ATVBAHA.109.193896. PubMed PMID:19834108.
102. Sun H, Wang Y. Interferon regulatory factors in heart:stress response beyond inflammation. Hypertension. 2014;63(4):663–664. Epub 2014/01/08. doi:10.1161/HYPERTENSIONAHA.113.02795 HYPERTENSIONAHA.113.02795 [pii]. PubMed PMID:24396026; PubMed Central PMCID:PMC4046326.
103. Doring Y, Soehnlein O, Drechsler M, Hematopoietic interferon regulatory factor 8-deficiency accelerates atherosclerosis in mice. Arterioscler Thromb Vasc Biol. 2012;32(7):1613–1623. Epub 2012/05/05. doi:10.1161/ATVBAHA.111.236539 ATVBAHA.111.236539 [pii]. PubMed PMID:22556330.
104. Leonard D, Svenungsson E, Sandling JK, Coronary heart disease in systemic lupus erythematosus is associated with interferon regulatory factor-8 gene variants. Circ Cardiovasc Genet. 2013;6(3):255–263. doi:10.1161/CIRCGENETICS.113.000044. PubMed PMID:23661672.
105. Zhang SM, Gao L, Zhang XF, Interferon regulatory factor 8 modulates phenotypic switching of smooth muscle cells by regulating the activity of myocardin. Mol Cell Biol. 2014;34(3):400–414. Epub 2013/11/20. doi:10.1128/MCB.01070-13 MCB.01070-13 [pii]. PubMed PMID:24248596; PubMed Central PMCID:PMC3911522.
106. Jiang DS, Wei X, Zhang XF, IRF8 suppresses pathological cardiac remodelling by inhibiting calcineurin signalling. Nat Commun. 2014;5:3303. Epub 2014/02/15. doi:10.1038/ncomms4303 ncomms4303 [pii]. PubMed PMID:24526256; PubMed Central PMCID:PMC3929801.
107. Kuhlencordt PJ, Chen J, Han F, Astern J, Huang PL. Genetic deficiency of inducible nitric oxide synthase reduces atherosclerosis and lowers plasma lipid peroxides in apolipoprotein E-knockout mice. Circulation. 2001;103(25):3099–3104. Epub 2001/06/27. PubMed PMID:11425775.
108. Niu XL, Yang X, Hoshiai K, Inducible nitric oxide synthase deficiency does not affect the susceptibility of mice to atherosclerosis but increases collagen content in lesions. Circulation. 2001;103(8):1115–1120. Epub 2001/02/27. PubMed PMID:11222475.
109. Martin-Ventura JL, Madrigal-Matute J, Munoz-Garcia B, Increased CD74 expression in human atherosclerotic plaques:contribution to inflammatory responses in vascular cells. Cardiovasc Res. 2009;83(3):586–594. Epub 2009/05/09. doi:10.1093/cvr/cvp141 cvp141 [pii]. PubMed PMID:19423618.
110. Eid RE, Rao DA, Zhou J, Interleukin-17 and interferon-gamma are produced concomitantly by human coronary artery-infiltrating T cells and act synergistically on vascular smooth muscle cells. Circulation. 2009;119(10):1424–1432. Epub 2009/03/04. doi:10.1161/CIRCULATIONAHA.108.827618 CIRCULATIONAHA.108.827618 [pii]. PubMed PMID:19255340; PubMed Central PMCID:PMC2898514.
111. Miklossy G, Hilliard TS, Turkson J. Therapeutic modulators of STAT signalling for human diseases. Nat Rev Drug Discov. 2013;12(8):611–629. Epub 2013/08/02. doi:10.1038/nrd4088 nrd4088 [pii]. PubMed PMID:23903221; PubMed Central PMCID:PMC4038293.
112. Song H, Wang R, Wang S, Lin J. A low-molecular-weight compound discovered through virtual database screening inhibits Stat3 function in breast cancer cells. Proc Natl Acad Sci USA. 2005;102(13):4700–4705. doi:10.1073/pnas.0409894102. PubMed PMID:15781862; PubMed Central PMCID:PMC555708.
113. McMurray JS. A new small-molecule Stat3 inhibitor. Chem Biol. 2006;13(11):1123–1124. doi:10.1016/j.chembiol.2006.11.001. PubMed PMID:17113993.
114. Szelag M, Czerwoniec A, Wesoly J, Bluyssen HA. Identification of STAT1 and STAT3 specific inhibitors using comparative virtual screening and docking validation. PloS one. 2015;10(2):e0116688. doi:10.1371/journal.pone.0116688. PubMed PMID:25710482; PubMed Central PMCID:PMC4339377.
115. Szelag M, Sikorski K, Czerwoniec A, Szatkowska K, Wesoly J, Bluyssen HA. In silico simulations of STAT1 and STAT3 inhibitors predict SH2 domain cross-binding specificity. Eur J Pharmacol. 2013;720(1–3):38–48. Epub 2013/11/12. doi:10.1016/j.ejphar.2013.10.055 S0014-2999(13)00822-4 [pii]. PubMed PMID:24211327.
116. Johnson AW, Kinzenbaw DA, Modrick ML, 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(2):437–442. Epub 2012/12/26. doi:10.1161/HYPERTENSIONAHA.111.00299 HYPERTENSIONAHA.111.00299 [pii]. PubMed PMID:23266544; PubMed Central PMCID:PMC3589547.
117. King VL, Lin AY, Kristo F, Interferon-gamma and the interferon-inducible chemokine CXCL10 protect against aneurysm formation and rupture. Circulation. 2009;119(3):426–435. Epub 2009/01/14. doi:CIRCULATIONAHA.108.785949 [pii] 10.1161/CIRCULATIONAHA.108.785949. PubMed PMID:19139386; PubMed Central PMCID:PMC2765043.
118. Eagleton MJ, Xu J, Liao M, Parine B, Chisolm GM, Graham LM. Loss of STAT1 is associated with increased aortic rupture in an experimental model of aortic dissection and aneurysm formation. J Vasc Surg. 2010;51(4):951–961; discussion 61. Epub 2010/03/30. doi:S0741-5214(09)02448-3 [pii] 10.1016/j.jvs.2009.11.075. PubMed PMID:20347693; PubMed Central PMCID:PMC2847593.
119. Soltesz B, Toth B, Shabashova N, New and recurrent gain-of-function STAT1 mutations in patients with chronic mucocutaneous candidiasis from Eastern and Central Europe. J Med Genet. 2013;50(9):567–578. Epub 2013/05/28. doi:10.1136/jmedgenet-2013-101570 jmedgenet-2013-101570 [pii]. PubMed PMID:23709754; PubMed Central PMCID:PMC3756505.
120. Szelag M, Czerwoniec A, Wesoly J, Bluyssen HA. Comparative screening and validation as a novel tool to identify STAT-specific inhibitors. Eur J Pharmacol. 2014;740:417–420. Epub 2014/09/04. doi:10.1016/j.ejphar.2014.05.047 S0014-2999(14)00409-9 [pii]. PubMed PMID:25183399.
121. Sikorski K, Wesoly J, Bluyssen H. Data mining of atherosclerotic plaque transcriptomes predicts STAT1-Dependent Inflammatory signal integration in vascular disease. Int J Mol Sci. 2014;15(8):14313–14331. PubMed PMID:doi:10.3390/ijms150814313.
122. You YN, Rustin RB, Sullivan JD. Oncotype DX colon cancer assay for prediction of recurrence risk in patients with stage II and III colon cancer:A review of the evidence. Surg Oncol. 2015. doi:10.1016/j.suronc.2015.02.001. PubMed PMID:25770397.
123. Yamani MH, Taylor DO, Haire C, Post-transplant ischemic injury is associated with up-regulated AlloMap gene expression. Clin Transplant. 2007;21(4):523–525. doi:10.1111/j.1399-0012.2007.00681.x. PubMed PMID:17645713.
124. Herder C, Baumert J, Zierer A, Immunological and cardiometabolic risk factors in the prediction of type 2 diabetes and coronary events:MONICA/KORA Augsburg case-cohort study. PLoS One. 2011;6(6):e19852. Epub 2011/06/16. doi:10.1371/journal.pone.0019852 PONE-D-10-05396 [pii]. PubMed PMID:21674000; PubMed Central PMCID:PMC3108947.
125. Khatri P, Roedder S, Kimura N, De Vusser K, Morgan AA, Gong Y, A common rejection module (CRM) for acute rejection across multiple organs identifies novel therapeutics for organ transplantation. J Exp Med. 2013;210(11):2205–2221. Epub 2013/10/16. doi:10.1084/jem.20122709 jem.20122709 [pii]. PubMed PMID:24127489; PubMed Central PMCID:PMC3804941.