The Inflammatory Kinase MAP4K4 Promotes Reactivation of Kaposi's Sarcoma Herpesvirus and Enhances the Invasiveness of Infected Endothelial Cells

PLoS Pathogens

Volumn 9, Issue 11, 2013, Pages

  Haas, Darya A ^a   Bala, Kiran ^a   Büsche, Guntram ^a   Weidner Glunde, Magdalena ^a   Santag, Susann ^a   Kati, Semra ^a   Gramolelli, Silvia ^a   Damas, Modester ^a   Dittrich Breiholz, Oliver ^a   Kracht, Michael ^b   Rückert, Jessica ^a   Varga, Zoltan ^c   Keri, György ^c,d   Schulz, Thomas F ^a  

^a HANNOVER MEDICAL SCHOOL   (Germany)

^b JUSTUS LIEBIG UNIVERSITY GIESSEN   (Germany)

^c Vichem Chemie Research Ltd   (Hungary)

^d SEMMELWEIS UNIVERSITY   (Hungary)

Author keywords

[No Author keywords available]

Indexed keywords

C REACTIVE PROTEIN; COLLAGENASE 3; CYCLOOXYGENASE 2; INTERLEUKIN 6; MATRILYSIN; MESSENGER RNA; METALLOPROTEINASE; MITOGEN ACTIVATED PROTEIN KINASE 4; SMALL INTERFERING RNA;

ARTICLE; CELL INVASION; CONTROLLED STUDY; ENZYME ACTIVITY; GENE DOSAGE; GENETIC TRANSFECTION; HUMAN; HUMAN CELL; HUMAN HERPESVIRUS 8; HUMAN TISSUE; IMMUNOHISTOCHEMISTRY; MICROARRAY ANALYSIS; NUCLEOTIDE SEQUENCE; PROTEIN EXPRESSION; PROTEIN PHOSPHORYLATION; REAL TIME POLYMERASE CHAIN REACTION; TUMOR INVASION; VIRUS REACTIVATION; VIRUS REPLICATION; WESTERN BLOTTING;

CYCLOOXYGENASE 2; ENDOTHELIAL CELLS; FEMALE; GENE EXPRESSION REGULATION, ENZYMOLOGIC; GENE EXPRESSION REGULATION, NEOPLASTIC; HEK293 CELLS; HERPESVIRUS 8, HUMAN; HUMANS; INFLAMMATION; INTRACELLULAR SIGNALING PEPTIDES AND PROTEINS; MALE; MATRIX METALLOPROTEINASE 13; MATRIX METALLOPROTEINASE 7; NEOPLASM INVASIVENESS; NEOPLASM PROTEINS; PROTEIN-SERINE-THREONINE KINASES; SARCOMA, KAPOSI; VIRUS ACTIVATION;

EID: 84888236296     PISSN: 15537366     EISSN: 15537374     Source Type: Journal    
DOI: 10.1371/journal.ppat.1003737     Document Type: Article

References (138)

1. Chang Y, Cesarman E, Pessin MS, Lee F, Culpepper J, et al. (1994) Identification of herpesvirus-like DNA sequences in AIDS-associated Kaposi's sarcoma. Science 266: 1865-1869.
2. Hengge UR, Ruzicka T, Tyring SK, Stuschke M, Roggendorf M, et al. (2002) Update on Kaposi's sarcoma and other HHV8 associated diseases. Part 1: epidemiology, environmental predispositions, clinical manifestations, and therapy. Lancet Infect Dis 2: 281-292.
3. Hengge UR, Ruzicka T, Tyring SK, Stuschke M, Roggendorf M, et al. (2002) Update on Kaposi's sarcoma and other HHV8 associated diseases. Part 2: pathogenesis, Castleman's disease, and pleural effusion lymphoma. Lancet Infect Dis 2: 344-352.
4. Chung YH, Means RE, Choi JK, Lee BS, Jung JU, (2002) Kaposi's sarcoma-associated herpesvirus OX2 glycoprotein activates myeloid-lineage cells to induce inflammatory cytokine production. J Virol 76: 4688-4698.
5. Ganem D, (2006) KSHV infection and the pathogenesis of Kaposi's sarcoma. Annu Rev Pathol 1: 273-296.
6. Schulz TF, (2006) The pleiotropic effects of Kaposi's sarcoma herpesvirus. J Pathol 208: 187-198.
7. Said JW, Tasaka T, Takeuchi S, Asou H, de Vos S, et al. (1996) Primary effusion lymphoma in women: report of two cases of Kaposi's sarcoma herpes virus-associated effusion-based lymphoma in human immunodeficiency virus-negative women. Blood 88: 3124-3128.
8. Soulier J, Grollet L, Oksenhendler E, Cacoub P, Cazals-Hatem D, et al. (1995) Kaposi's sarcoma-associated herpesvirus-like DNA sequences in multicentric Castleman's disease. Blood 86: 1276-1280.
9. Ensoli B, Sturzl M, (1998) Kaposi's sarcoma: a result of the interplay among inflammatory cytokines, angiogenic factors and viral agents. Cytokine Growth Factor Rev 9: 63-83.
10. Grossmann C, Podgrabinska S, Skobe M, Ganem D, (2006) Activation of NF-kappaB by the latent vFLIP gene of Kaposi's sarcoma-associated herpesvirus is required for the spindle shape of virus-infected endothelial cells and contributes to their proinflammatory phenotype. J Virol 80: 7179-7185.
11. Pyakurel P, Pak F, Mwakigonja AR, Kaaya E, Heiden T, et al. (2006) Lymphatic and vascular origin of Kaposi's sarcoma spindle cells during tumor development. Int J Cancer 119: 1262-1267.
12. Dupin N, Fisher C, Kellam P, Ariad S, Tulliez M, et al. (1999) Distribution of human herpesvirus-8 latently infected cells in Kaposi's sarcoma, multicentric Castleman's disease, and primary effusion lymphoma. Proc Natl Acad Sci U S A 96: 4546-4551.
13. Rosano L, Spinella F, Di Castro V, Nicotra MR, Albini A, et al. (2003) Endothelin receptor blockade inhibits molecular effectors of Kaposi's sarcoma cell invasion and tumor growth in vivo. Am J Pathol 163: 753-762.
14. Pantanowitz L, Dezube BJ, Hernandez-Barrantes S, Tahan SR, Dabbous MK, (2006) Matrix metalloproteinases in the progression and regression of Kaposi's sarcoma. J Cutan Pathol 33: 793-798.
15. Blankaert D, Simonart T, Van Vooren JP, Parent D, Liesnard C, et al. (1998) Constitutive release of metalloproteinase-9 (92-kd type IV collagenase) by Kaposi's sarcoma cells. J Acquir Immune Defic Syndr Hum Retrovirol 18: 203-209.
16. Qian LW, Xie J, Ye F, Gao SJ, (2007) Kaposi's sarcoma-associated herpesvirus infection promotes invasion of primary human umbilical vein endothelial cells by inducing matrix metalloproteinases. J Virol 81: 7001-7010.
17. Fingleton B, Matrisian LM, (2001) Matrix metalloproteinases as targets for therapy in Kaposi sarcoma. Curr Opin Oncol 13: 368-373.
18. Deryugina EI, Quigley JP, (2006) Matrix metalloproteinases and tumor metastasis. Cancer Metastasis Rev 25: 9-34.
19. Simmons DL, Botting RM, Hla T, (2004) Cyclooxygenase isozymes: the biology of prostaglandin synthesis and inhibition. Pharmacol Rev 56: 387-437.
20. Sharma-Walia N, Paul AG, Bottero V, Sadagopan S, Veettil MV, et al. (2010) Kaposi's sarcoma associated herpes virus (KSHV) induced COX-2: a key factor in latency, inflammation, angiogenesis, cell survival and invasion. PLoS Pathog 6: e1000777.
21. Lu H, Ouyang W, Huang C, (2006) Inflammation, a key event in cancer development. Mol Cancer Res 4: 221-233.
22. Sales KJ, Katz AA, Howard B, Soeters RP, Millar RP, et al. (2002) Cyclooxygenase-1 is up-regulated in cervical carcinomas: autocrine/paracrine regulation of cyclooxygenase-2, prostaglandin e receptors, and angiogenic factors by cyclooxygenase-1. Cancer Res 62: 424-432.
23. Naranatt PP, Krishnan HH, Svojanovsky SR, Bloomer C, Mathur S, et al. (2004) Host gene induction and transcriptional reprogramming in Kaposi's sarcoma-associated herpesvirus (KSHV/HHV-8)-infected endothelial, fibroblast, and B cells: insights into modulation events early during infection. Cancer Res 64: 72-84.
24. Sharma-Walia N, Raghu H, Sadagopan S, Sivakumar R, Veettil MV, et al. (2006) Cyclooxygenase 2 induced by Kaposi's sarcoma-associated herpesvirus early during in vitro infection of target cells plays a role in the maintenance of latent viral gene expression. J Virol 80: 6534-6552.
25. Brinkmann MM, Pietrek M, Dittrich-Breiholz O, Kracht M, Schulz TF, (2007) Modulation of host gene expression by the K15 protein of Kaposi's sarcoma-associated herpesvirus. J Virol 81: 42-58.
26. Shelby BD, LaMarca HL, McFerrin HE, Nelson AB, Lasky JA, et al. (2007) Kaposi's sarcoma associated herpesvirus G-protein coupled receptor activation of cyclooxygenase-2 in vascular endothelial cells. Virol J 4: 87.
27. Ganem D, (2010) KSHV and the pathogenesis of Kaposi sarcoma: listening to human biology and medicine. J Clin Invest 120: 939-949.
28. Giraldo G, Beth E, Huang ES, (1980) Kaposi's sarcoma and its relationship to cytomegalovirus (CMNV). III. CMV DNA and CMV early antigens in Kaposi's sarcoma. Int J Cancer 26: 23-29.
29. Moore PS, Chang Y, (2001) Molecular virology of Kaposi's sarcoma-associated herpesvirus. Philos Trans R Soc Lond B Biol Sci 356: 499-516.
30. Nicholas J, (2005) Human gammaherpesvirus cytokines and chemokine receptors. J Interferon Cytokine Res 25: 373-383.
31. Greene W, Kuhne K, Ye F, Chen J, Zhou F, et al. (2007) Molecular biology of KSHV in relation to AIDS-associated oncogenesis. Cancer Treat Res 133: 69-127.
32. Martin JN, Osmond DH, (1999) Kaposi's sarcoma-associated herpesvirus and sexual transmission of cancer risk. Curr Opin Oncol 11: 508-515.
33. Grundhoff A, Ganem D, (2004) Inefficient establishment of KSHV latency suggests an additional role for continued lytic replication in Kaposi sarcoma pathogenesis. J Clin Invest 113: 124-136.
34. Au WW, Callaham MF, Workman ML, Huberman E, (1983) Double minute chromatin bodies and other chromosome alterations in human myeloid HL-60 leukemia cells susceptible or resistant to induction of differentiation by phorbol-12-myristate-13-acetate. Cancer Res 43: 5873-5878.
35. Kitzis A, Tichonicky L, Defer N, Kruh J, (1980) Effect of sodium butyrate on chromatin structure. Biochem Biophys Res Commun 93: 833-841.
36. Lu F, Zhou J, Wiedmer A, Madden K, Yuan Y, et al. (2003) Chromatin remodeling of the Kaposi's sarcoma-associated herpesvirus ORF50 promoter correlates with reactivation from latency. J Virol 77: 11425-11435.
37. Lukac DM, Renne R, Kirshner JR, Ganem D, (1998) Reactivation of Kaposi's sarcoma-associated herpesvirus infection from latency by expression of the ORF 50 transactivator, a homolog of the EBV R protein. Virology 252: 304-312.
38. Deutsch E, Cohen A, Kazimirsky G, Dovrat S, Rubinfeld H, et al. (2004) Role of protein kinase C delta in reactivation of Kaposi's sarcoma-associated herpesvirus. J Virol 78: 10187-10192.
39. Ford PW, Bryan BA, Dyson OF, Weidner DA, Chintalgattu V, et al. (2006) Raf/MEK/ERK signalling triggers reactivation of Kaposi's sarcoma-associated herpesvirus latency. J Gen Virol 87: 1139-1144.
40. Chang H, Dittmer DP, Shin YC, Hong Y, Jung JU, (2005) Role of Notch signal transduction in Kaposi's sarcoma-associated herpesvirus gene expression. J Virol 79: 14371-14382.
41. Lan K, Murakami M, Choudhuri T, Kuppers DA, Robertson ES, (2006) Intracellular-activated Notch1 can reactivate Kaposi's sarcoma-associated herpesvirus from latency. Virology 351: 393-403.
42. Liang Y, Chang J, Lynch SJ, Lukac DM, Ganem D, (2002) The lytic switch protein of KSHV activates gene expression via functional interaction with RBP-Jkappa (CSL), the target of the Notch signaling pathway. Genes Dev 16: 1977-1989.
43. Xie J, Ajibade AO, Ye F, Kuhne K, Gao SJ, (2008) Reactivation of Kaposi's sarcoma-associated herpesvirus from latency requires MEK/ERK, JNK and p38 multiple mitogen-activated protein kinase pathways. Virology 371: 139-154.
44. Cheng F, Weidner-Glunde M, Varjosalo M, Rainio EM, Lehtonen A, et al. (2009) KSHV reactivation from latency requires Pim-1 and Pim-3 kinases to inactivate the latency-associated nuclear antigen LANA. PLoS Pathog 5: e1000324.
45. Qin D, Feng N, Fan W, Ma X, Yan Q, et al. (2011) Activation of PI3K/AKT and ERK MAPK signal pathways is required for the induction of lytic cycle replication of Kaposi's sarcoma-associated herpesvirus by herpes simplex virus type 1. BMC Microbiol 11: 240.
46. Gregory SM, West JA, Dillon PJ, Hilscher C, Dittmer DP, et al. (2009) Toll-like receptor signaling controls reactivation of KSHV from latency. Proc Natl Acad Sci U S A 106: 11725-11730.
47. Aouadi M, Tesz GJ, Nicoloro SM, Wang M, Chouinard M, et al. (2009) Orally delivered siRNA targeting macrophage Map4k4 suppresses systemic inflammation. Nature 458: 1180-1184.
48. Bouzakri K, Zierath JR, (2007) MAP4K4 gene silencing in human skeletal muscle prevents tumor necrosis factor-alpha-induced insulin resistance. J Biol Chem 282: 7783-7789.
49. Collins CS, Hong J, Sapinoso L, Zhou Y, Liu Z, et al. (2006) A small interfering RNA screen for modulators of tumor cell motility identifies MAP4K4 as a promigratory kinase. Proc Natl Acad Sci U S A 103: 3775-3780.
50. Liang JJ, Wang H, Rashid A, Tan TH, Hwang RF, et al. (2008) Expression of MAP4K4 is associated with worse prognosis in patients with stage II pancreatic ductal adenocarcinoma. Clin Cancer Res 14: 7043-7049.
51. Liu AW, Cai J, Zhao XL, Jiang TH, He TF, et al. (2011) ShRNA-targeted MAP4K4 inhibits hepatocellular carcinoma growth. Clin Cancer Res 17: 710-720.
52. Puri V, Virbasius JV, Guilherme A, Czech MP, (2008) RNAi screens reveal novel metabolic regulators: RIP140, MAP4k4 and the lipid droplet associated fat specific protein (FSP) 27. Acta Physiol (Oxf) 192: 103-115.
53. Tesz GJ, Guilherme A, Guntur KV, Hubbard AC, Tang X, et al. (2007) Tumor necrosis factor alpha (TNFalpha) stimulates Map4k4 expression through TNFalpha receptor 1 signaling to c-Jun and activating transcription factor 2. J Biol Chem 282: 19302-19312.
54. Tang X, Guilherme A, Chakladar A, Powelka AM, Konda S, et al. (2006) An RNA interference-based screen identifies MAP4K4/NIK as a negative regulator of PPARgamma, adipogenesis, and insulin-responsive hexose transport. Proc Natl Acad Sci U S A 103: 2087-2092.
55. Guntur KV, Guilherme A, Xue L, Chawla A, Czech MP, (2010) Map4k4 negatively regulates peroxisome proliferator-activated receptor (PPAR) gamma protein translation by suppressing the mammalian target of rapamycin (mTOR) signaling pathway in cultured adipocytes. J Biol Chem 285: 6595-6603.
56. Campbell TB, Borok M, White IE, Gudza I, Ndemera B, et al. (2003) Relationship of Kaposi sarcoma (KS)-associated herpesvirus viremia and KS disease in Zimbabwe. Clin Infect Dis 36: 1144-1151.
57. Humphrey RW, O'Brien TR, Newcomb FM, Nishihara H, Wyvill KM, et al. (1996) Kaposi's sarcoma (KS)-associated herpesvirus-like DNA sequences in peripheral blood mononuclear cells: association with KS and persistence in patients receiving anti-herpesvirus drugs. Blood 88: 297-301.
58. Pan H, Xie J, Ye F, Gao SJ, (2006) Modulation of Kaposi's sarcoma-associated herpesvirus infection and replication by MEK/ERK, JNK, and p38 multiple mitogen-activated protein kinase pathways during primary infection. J Virol 80: 5371-5382.
59. Jarviluoma A, Ojala PM, (2006) Cell signaling pathways engaged by KSHV. Biochim Biophys Acta 1766: 140-158.
60. Vieira J, O'Hearn PM, (2004) Use of the red fluorescent protein as a marker of Kaposi's sarcoma-associated herpesvirus lytic gene expression. Virology 325: 225-240.
61. Briot D, Mace-Aime G, Subra F, Rosselli F, (2008) Aberrant activation of stress-response pathways leads to TNF-alpha oversecretion in Fanconi anemia. Blood 111: 1913-1923.
62. Edgell CJ, McDonald CC, Graham JB, (1983) Permanent cell line expressing human factor VIII-related antigen established by hybridization. Proc Natl Acad Sci U S A 80: 3734-3737.
63. Karaman MW, Herrgard S, Treiber DK, Gallant P, Atteridge CE, et al. (2008) A quantitative analysis of kinase inhibitor selectivity. Nat Biotechnol 26: 127-132.
64. Yao Z, Zhou G, Wang XS, Brown A, Diener K, et al. (1999) A novel human STE20-related protein kinase, HGK, that specifically activates the c-Jun N-terminal kinase signaling pathway. J Biol Chem 274: 2118-2125.
65. Mack FA, Patel JH, Biju MP, Haase VH, Simon MC, (2005) Decreased growth of Vhl-/- fibrosarcomas is associated with elevated levels of cyclin kinase inhibitors p21 and p27. Mol Cell Biol 25: 4565-4578.
66. Chatterjee M, Osborne J, Bestetti G, Chang Y, Moore PS, (2002) Viral IL-6-induced cell proliferation and immune evasion of interferon activity. Science 298: 1432-1435.
67. Kedes DH, Ganem D, (1997) Sensitivity of Kaposi's sarcoma-associated herpesvirus replication to antiviral drugs. Implications for potential therapy. J Clin Invest 99: 2082-2086.
68. Baumgartner M, Sillman AL, Blackwood EM, Srivastava J, Madson N, et al. (2006) The Nck-interacting kinase phosphorylates ERM proteins for formation of lamellipodium by growth factors. Proc Natl Acad Sci U S A 103: 13391-13396.
69. Simonart T, Degraef C, Mosselmans R, Hermans P, Lunardi-Iskandar Y, et al. (2001) Early- and late-stage Kaposi's sarcoma-derived cells but not activated endothelial cells can invade de-epidermized dermis. J Invest Dermatol 116: 679-685.
70. Alkharsah KR, Singh VV, Bosco R, Santag S, Grundhoff A, et al. (2011) Deletion of Kaposi's sarcoma-associated herpesvirus FLICE inhibitory protein, vFLIP, from the viral genome compromises the activation of STAT1-responsive cellular genes and spindle cell formation in endothelial cells. J Virol 85: 10375-10388.
71. Bongiorno MR, Doukaki S, Ferro G, Arico M, (2010) Matrix metalloproteinases 2 and 9, and extracellular matrix in Kaposi's sarcoma. Dermatol Ther 23 Suppl 2: S33-36.
72. Meade-Tollin LC, Way D, Witte MH, (1999) Expression of multiple matrix metalloproteinases and urokinase type plasminogen activator in cultured Kaposi sarcoma cells. Acta Histochem 101: 305-316.
73. Yamamoto N, Bryce NS, Metzler-Nolte N, Hambley TW, (2012) Effects of Enzymatic Activation on the Distribution of Fluorescently Tagged MMP-2 Cleavable Peptides in Cancer Cells and Spheroids. Bioconjug Chem [epub ahead of print].
74. Beeghly-Fadiel A, Long JR, Gao YT, Li C, Qu S, et al. (2008) Common MMP-7 polymorphisms and breast cancer susceptibility: a multistage study of association and functionality. Cancer Res 68: 6453-6459.
75. Shiomi T, Okada Y, (2003) MT1-MMP and MMP-7 in invasion and metastasis of human cancers. Cancer Metastasis Rev 22: 145-152.
76. Lee SK, Han YM, Yun J, Lee CW, Shin DS, et al. (2012) Phosphatase of regenerating liver-3 promotes migration and invasion by upregulating matrix metalloproteinases-7 in human colorectal cancer cells. Int J Cancer 131: E190-203.
77. Wang FQ, Smicun Y, Calluzzo N, Fishman DA, (2006) Inhibition of matrilysin expression by antisense or RNA interference decreases lysophosphatidic acid-induced epithelial ovarian cancer invasion. Mol Cancer Res 4: 831-841.
78. Yue W, Sun Q, Landreneau R, Wu C, Siegfried JM, et al. (2009) Fibulin-5 suppresses lung cancer invasion by inhibiting matrix metalloproteinase-7 expression. Cancer Res 69: 6339-6346.
79. Ala-Aho R, Johansson N, Baker AH, Kahari VM, (2002) Expression of collagenase-3 (MMP-13) enhances invasion of human fibrosarcoma HT-1080 cells. Int J Cancer 97: 283-289.
80. Fournier T, Fadok V, Henson PM, (1997) Tumor necrosis factor-alpha inversely regulates prostaglandin D2 and prostaglandin E2 production in murine macrophages. Synergistic action of cyclic AMP on cyclooxygenase-2 expression and prostaglandin E2 synthesis. J Biol Chem 272: 31065-31072.
81. Greenhough A, Smartt HJ, Moore AE, Roberts HR, Williams AC, et al. (2009) The COX-2/PGE2 pathway: key roles in the hallmarks of cancer and adaptation to the tumour microenvironment. Carcinogenesis 30: 377-386.
82. Qiu MH, Qian YM, Zhao XL, Wang SM, Feng XJ, et al. (2012) Expression and prognostic significance of MAP4K4 in lung adenocarcinoma. Pathol Res Pract 208: 541-548.
83. Katano H, Sato Y, Kurata T, Mori S, Sata T, (2000) Expression and localization of human herpesvirus 8-encoded proteins in primary effusion lymphoma, Kaposi's sarcoma, and multicentric Castleman's disease. Virology 269: 335-344.
84. Cheng F, Pekkonen P, Laurinavicius S, Sugiyama N, Henderson S, et al. (2011) KSHV-initiated notch activation leads to membrane-type-1 matrix metalloproteinase-dependent lymphatic endothelial-to-mesenchymal transition. Cell Host Microbe 10: 577-590.
85. Fonsato V, Buttiglieri S, Deregibus MC, Bussolati B, Caselli E, et al. (2008) PAX2 expression by HHV-8-infected endothelial cells induced a proangiogenic and proinvasive phenotype. Blood 111: 2806-2815.
86. Sadagopan S, Sharma-Walia N, Veettil MV, Bottero V, Levine R, et al. (2009) Kaposi's sarcoma-associated herpesvirus upregulates angiogenin during infection of human dermal microvascular endothelial cells, which induces 45S rRNA synthesis, antiapoptosis, cell proliferation, migration, and angiogenesis. J Virol 83: 3342-3364.
87. Dillon PJ, Gregory SM, Tamburro K, Sanders MK, Johnson GL, et al. (2013) Tousled-like kinases modulate reactivation of gammaherpesviruses from latency. Cell Host Microbe 13: 204-214.
88. Naranatt PP, Akula SM, Zien CA, Krishnan HH, Chandran B, (2003) Kaposi's sarcoma-associated herpesvirus induces the phosphatidylinositol 3-kinase-PKC-zeta-MEK-ERK signaling pathway in target cells early during infection: implications for infectivity. J Virol 77: 1524-1539.
89. Sodhi A, Montaner S, Patel V, Zohar M, Bais C, et al. (2000) The Kaposi's sarcoma-associated herpes virus G protein-coupled receptor up-regulates vascular endothelial growth factor expression and secretion through mitogen-activated protein kinase and p38 pathways acting on hypoxia-inducible factor 1alpha. Cancer Res 60: 4873-4880.
90. Gallagher TF, Seibel GL, Kassis S, Laydon JT, Blumenthal MJ, et al. (1997) Regulation of stress-induced cytokine production by pyridinylimidazoles; inhibition of CSBP kinase. Bioorg Med Chem 5: 49-64.
91. Jackson JR, Bolognese B, Hillegass L, Kassis S, Adams J, et al. (1998) Pharmacological effects of SB 220025, a selective inhibitor of P38 mitogen-activated protein kinase, in angiogenesis and chronic inflammatory disease models. J Pharmacol Exp Ther 284: 687-692.
92. Lee JC, Kassis S, Kumar S, Badger A, Adams JL, (1999) p38 mitogen-activated protein kinase inhibitors-mechanisms and therapeutic potentials. Pharmacol Ther 82: 389-397.
93. Boehm JC, Bower MJ, Gallagher TF, Kassis S, Johnson SR, et al. (2001) Phenoxypyrimidine inhibitors of p38alpha kinase: synthesis and statistical evaluation of the p38 inhibitory potencies of a series of 1-(piperidin-4-yl)-4-(4-fluorophenyl)-5-(2-phenoxypyrimidin-4-yl) imidazoles. Bioorg Med Chem Lett 11: 1123-1126.
94. Edraki N, Hemmateenejad B, Miri R, Khoshneviszade M, (2007) QSAR study of Phenoxypyrimidine Derivatives as Potent Inhibitors of p38 Kinase using different chemometric tools. Chem Biol Drug Des 70: 530-539.
95. Fabian MA, Biggs WH 3rd, Treiber DK, Atteridge CE, Azimioara MD, et al. (2005) A small molecule-kinase interaction map for clinical kinase inhibitors. Nat Biotechnol 23: 329-336.
96. Pouliot M, Baillargeon J, Lee JC, Cleland LG, James MJ, (1997) Inhibition of prostaglandin endoperoxide synthase-2 expression in stimulated human monocytes by inhibitors of p38 mitogen-activated protein kinase. J Immunol 158: 4930-4937.
97. Lee JC, Badger AM, Griswold DE, Dunnington D, Truneh A, et al. (1993) Bicyclic imidazoles as a novel class of cytokine biosynthesis inhibitors. Ann N Y Acad Sci 696: 149-170.
98. Cuenda A, Rouse J, Doza YN, Meier R, Cohen P, et al. (1995) SB 203580 is a specific inhibitor of a MAP kinase homologue which is stimulated by cellular stresses and interleukin-1. FEBS Lett 364: 229-233.
99. Manning AM, Davis RJ, (2003) Targeting JNK for therapeutic benefit: from junk to gold? Nat Rev Drug Discov 2: 554-565.
100. Rincon M, Davis RJ, (2009) Regulation of the immune response by stress-activated protein kinases. Immunol Rev 228: 212-224.
101. Xie J, Pan H, Yoo S, Gao SJ, (2005) Kaposi's sarcoma-associated herpesvirus induction of AP-1 and interleukin 6 during primary infection mediated by multiple mitogen-activated protein kinase pathways. J Virol 79: 15027-15037.
102. An J, Sun Y, Sun R, Rettig MB, (2003) Kaposi's sarcoma-associated herpesvirus encoded vFLIP induces cellular IL-6 expression: the role of the NF-kappaB and JNK/AP1 pathways. Oncogene 22: 3371-3385.
103. Paulose-Murphy M, Ha NK, Xiang C, Chen Y, Gillim L, et al. (2001) Transcription program of human herpesvirus 8 (kaposi's sarcoma-associated herpesvirus). J Virol 75: 4843-4853.
104. Kang JG, Majerciak V, Uldrick TS, Wang X, Kruhlak M, et al. (2011) Kaposi's sarcoma-associated herpesviral IL-6 and human IL-6 open reading frames contain miRNA binding sites and are subject to cellular miRNA regulation. J Pathol 225: 378-389.
105. Nindl I, Dang C, Forschner T, Kuban RJ, Meyer T, et al. (2006) Identification of differentially expressed genes in cutaneous squamous cell carcinoma by microarray expression profiling. Mol Cancer 5: 30.
106. Han SX, Zhu Q, Ma JL, Zhao J, Huang C, et al. (2010) Lowered HGK expression inhibits cell invasion and adhesion in hepatocellular carcinoma cell line HepG2. World J Gastroenterol 16: 4541-4548.
107. Ambrus JL, Stoll HL, Klein EA, Karakousis CP, Stadler S, (1992) Increased prostaglandin E2 and cAMP phosphodiesterase levels in Kaposi's sarcoma-a virus against host defense mechanism. Res Commun Chem Pathol Pharmacol 78: 249-252.
108. Gao SJ, Deng JH, Zhou FC, (2003) Productive lytic replication of a recombinant Kaposi's sarcoma-associated herpesvirus in efficient primary infection of primary human endothelial cells. J Virol 77: 9738-9749.
109. Zhu H, Cong JP, Yu D, Bresnahan WA, Shenk TE, (2002) Inhibition of cyclooxygenase 2 blocks human cytomegalovirus replication. Proc Natl Acad Sci U S A 99: 3932-3937.
110. Rott D, Zhu J, Burnett MS, Zhou YF, Zalles-Ganley A, et al. (2003) Effects of MF-tricyclic, a selective cyclooxygenase-2 inhibitor, on atherosclerosis progression and susceptibility to cytomegalovirus replication in apolipoprotein-E knockout mice. J Am Coll Cardiol 41: 1812-1819.
111. Kline JN, Hunninghake GM, He B, Monick MM, Hunninghake GW, (1998) Synergistic activation of the human cytomegalovirus major immediate early promoter by prostaglandin E2 and cytokines. Exp Lung Res 24: 3-14.
112. Janelle ME, Gravel A, Gosselin J, Tremblay MJ, Flamand L, (2002) Activation of monocyte cyclooxygenase-2 gene expression by human herpesvirus 6. Role for cyclic AMP-responsive element-binding protein and activator protein-1. J Biol Chem 277: 30665-30674.
113. Symensma TL, Martinez-Guzman D, Jia Q, Bortz E, Wu TT, et al. (2003) COX-2 induction during murine gammaherpesvirus 68 infection leads to enhancement of viral gene expression. J Virol 77: 12753-12763.
114. Khyatti M, Menezes J, (1990) The effect of indomethacin, prostaglandin E2 and interferon on the multiplication of herpes simplex virus type 1 in human lymphoid cells. Antiviral Res 14: 161-172.
115. Gatanaga T, Hwang CD, Kohr W, Cappuccini F, Lucci JA 3rd, et al. (1990) Purification and characterization of an inhibitor (soluble tumor necrosis factor receptor) for tumor necrosis factor and lymphotoxin obtained from the serum ultrafiltrates of human cancer patients. Proc Natl Acad Sci U S A 87: 8781-8784.
116. Ben-Av P, Crofford LJ, Wilder RL, Hla T, (1995) Induction of vascular endothelial growth factor expression in synovial fibroblasts by prostaglandin E and interleukin-1: a potential mechanism for inflammatory angiogenesis. FEBS Lett 372: 83-87.
117. Tsujii M, Kawano S, Tsuji S, Sawaoka H, Hori M, et al. (1998) Cyclooxygenase regulates angiogenesis induced by colon cancer cells. Cell 93: 705-716.
118. Sheng H, Shao J, Dubois RN, (2001) K-Ras-mediated increase in cyclooxygenase 2 mRNA stability involves activation of the protein kinase B1. Cancer Res 61: 2670-2675.
119. Hu KQ, Yu CH, Mineyama Y, McCracken JD, Hillebrand DJ, et al. (2003) Inhibited proliferation of cyclooxygenase-2 expressing human hepatoma cells by NS-398, a selective COX-2 inhibitor. Int J Oncol 22: 757-763.
120. Harris RE, (2007) Cyclooxygenase-2 (cox-2) and the inflammogenesis of cancer. Subcell Biochem 42: 93-126.
121. Tjiu JW, Chen JS, Shun CT, Lin SJ, Liao YH, et al. (2009) Tumor-associated macrophage-induced invasion and angiogenesis of human basal cell carcinoma cells by cyclooxygenase-2 induction. J Invest Dermatol 129: 1016-1025.
122. Legler DF, Bruckner M, Uetz-von Allmen E, Krause P, (2010) Prostaglandin E2 at new glance: novel insights in functional diversity offer therapeutic chances. Int J Biochem Cell Biol 42: 198-201.
123. Ra HJ, Harju-Baker S, Zhang F, Linhardt RJ, Wilson CL, et al. (2009) Control of promatrilysin (MMP7) activation and substrate-specific activity by sulfated glycosaminoglycans. J Biol Chem 284: 27924-27932.
124. Knauper V, Will H, Lopez-Otin C, Smith B, Atkinson SJ, et al. (1996) Cellular mechanisms for human procollagenase-3 (MMP-13) activation. Evidence that MT1-MMP (MMP-14) and gelatinase a (MMP-2) are able to generate active enzyme. J Biol Chem 271: 17124-17131.
125. Nagase H, Woessner JF Jr, (1999) Matrix metalloproteinases. J Biol Chem 274: 21491-21494.
126. Yan C, Boyd DD, (2007) Regulation of matrix metalloproteinase gene expression. J Cell Physiol 211: 19-26.
127. Ozanne BW, Spence HJ, McGarry LC, Hennigan RF, (2007) Transcription factors control invasion: AP-1 the first among equals. Oncogene 26: 1-10.
128. Liacini A, Sylvester J, Li WQ, Huang W, Dehnade F, et al. (2003) Induction of matrix metalloproteinase-13 gene expression by TNF-alpha is mediated by MAP kinases, AP-1, and NF-kappaB transcription factors in articular chondrocytes. Exp Cell Res 288: 208-217.
129. Mengshol JA, Vincenti MP, Brinckerhoff CE, (2001) IL-1 induces collagenase-3 (MMP-13) promoter activity in stably transfected chondrocytic cells: requirement for Runx-2 and activation by p38 MAPK and JNK pathways. Nucleic Acids Res 29: 4361-4372.
130. Wisithphrom K, Murray PE, Windsor LJ, (2006) Interleukin-1 alpha alters the expression of matrix metalloproteinases and collagen degradation by pulp fibroblasts. J Endod 32: 186-192.
131. Westermarck J, Kahari VM, (1999) Regulation of matrix metalloproteinase expression in tumor invasion. FASEB J 13: 781-792.
132. Jaffe EA, Nachman RL, Becker CG, Minick CR, (1973) Culture of human endothelial cells derived from umbilical veins. Identification by morphologic and immunologic criteria. J Clin Invest 52: 2745-2756.
133. May T, Butueva M, Bantner S, Markusic D, Seppen J, et al. (2010) Synthetic gene regulation circuits for control of cell expansion. Tissue Eng Part A 16: 441-452.
134. Milligan S, Robinson M, O'Donnell E, Blackbourn DJ, (2004) Inflammatory cytokines inhibit Kaposi's sarcoma-associated herpesvirus lytic gene transcription in in vitro-infected endothelial cells. J Virol 78: 2591-2596.
135. Xu Y, AuCoin DP, Huete AR, Cei SA, Hanson LJ, et al. (2005) A Kaposi's sarcoma-associated herpesvirus/human herpesvirus 8 ORF50 deletion mutant is defective for reactivation of latent virus and DNA replication. J Virol 79: 3479-3487.
136. Kati S, Tsao EH, Gunther T, Weidner-Glunde M, Rothamel T, et al. (2013) Activation of the B Cell Antigen Receptor Triggers Reactivation of Latent Kaposi's Sarcoma-Associated Herpesvirus in B Cells. J Virol 87: 8004-8016.
137. Carpenter AE, Jones TR, Lamprecht MR, Clarke C, Kang IH, et al. (2006) CellProfiler: image analysis software for identifying and quantifying cell phenotypes. Genome Biol 7: R100.
138. Otsu N, (1979) Threshold Selection Method from Gray-Level Histograms. Ieee Transactions on Systems Man and Cybernetics 9: 62-66.