Kaposi's Sarcoma Associated Herpes Virus (KSHV) Induced COX-2: A Key Factor in Latency, Inflammation, Angiogenesis, Cell Survival and Invasion


Kaposi's sarcoma (KS), an enigmatic endothelial cell vascular neoplasm, is characterized by the proliferation of spindle shaped endothelial cells, inflammatory cytokines (ICs), growth factors (GFs) and angiogenic factors. KSHV is etiologically linked to KS and expresses its latent genes in KS lesion endothelial cells. Primary infection of human micro vascular endothelial cells (HMVEC-d) results in the establishment of latent infection and reprogramming of host genes, and cyclooxygenase-2 (COX-2) is one of the highly up-regulated genes. Our previous study suggested a role for COX-2 in the establishment and maintenance of KSHV latency. Here, we examined the role of COX-2 in the induction of ICs, GFs, angiogenesis and invasive events occurring during KSHV de novo infection of endothelial cells. A significant amount of COX-2 was detected in KS tissue sections. Telomerase-immortalized human umbilical vein endothelial cells supporting KSHV stable latency (TIVE-LTC) expressed elevated levels of functional COX-2 and microsomal PGE2 synthase (m-PGES), and secreted the predominant eicosanoid inflammatory metabolite PGE2. Infected HMVEC-d and TIVE-LTC cells secreted a variety of ICs, GFs, angiogenic factors and matrix metalloproteinases (MMPs), which were significantly abrogated by COX-2 inhibition either by chemical inhibitors or by siRNA. The ability of these factors to induce tube formation of uninfected endothelial cells was also inhibited. PGE2, secreted early during KSHV infection, profoundly increased the adhesion of uninfected endothelial cells to fibronectin by activating the small G protein Rac1. COX-2 inhibition considerably reduced KSHV latent ORF73 gene expression and survival of TIVE-LTC cells. Collectively, these studies underscore the pivotal role of KSHV induced COX-2/PGE2 in creating KS lesion like microenvironment during de novo infection. Since COX-2 plays multiple roles in KSHV latent gene expression, which themselves are powerful mediators of cytokine induction, anti-apoptosis, cell survival and viral genome maintainence, effective inhibition of COX-2 via well-characterized clinically approved COX-2 inhibitors could potentially be used in treatment to control latent KSHV infection and ameliorate KS.


Vyšlo v časopise: Kaposi's Sarcoma Associated Herpes Virus (KSHV) Induced COX-2: A Key Factor in Latency, Inflammation, Angiogenesis, Cell Survival and Invasion. PLoS Pathog 6(2): e32767. doi:10.1371/journal.ppat.1000777
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1000777

Souhrn

Kaposi's sarcoma (KS), an enigmatic endothelial cell vascular neoplasm, is characterized by the proliferation of spindle shaped endothelial cells, inflammatory cytokines (ICs), growth factors (GFs) and angiogenic factors. KSHV is etiologically linked to KS and expresses its latent genes in KS lesion endothelial cells. Primary infection of human micro vascular endothelial cells (HMVEC-d) results in the establishment of latent infection and reprogramming of host genes, and cyclooxygenase-2 (COX-2) is one of the highly up-regulated genes. Our previous study suggested a role for COX-2 in the establishment and maintenance of KSHV latency. Here, we examined the role of COX-2 in the induction of ICs, GFs, angiogenesis and invasive events occurring during KSHV de novo infection of endothelial cells. A significant amount of COX-2 was detected in KS tissue sections. Telomerase-immortalized human umbilical vein endothelial cells supporting KSHV stable latency (TIVE-LTC) expressed elevated levels of functional COX-2 and microsomal PGE2 synthase (m-PGES), and secreted the predominant eicosanoid inflammatory metabolite PGE2. Infected HMVEC-d and TIVE-LTC cells secreted a variety of ICs, GFs, angiogenic factors and matrix metalloproteinases (MMPs), which were significantly abrogated by COX-2 inhibition either by chemical inhibitors or by siRNA. The ability of these factors to induce tube formation of uninfected endothelial cells was also inhibited. PGE2, secreted early during KSHV infection, profoundly increased the adhesion of uninfected endothelial cells to fibronectin by activating the small G protein Rac1. COX-2 inhibition considerably reduced KSHV latent ORF73 gene expression and survival of TIVE-LTC cells. Collectively, these studies underscore the pivotal role of KSHV induced COX-2/PGE2 in creating KS lesion like microenvironment during de novo infection. Since COX-2 plays multiple roles in KSHV latent gene expression, which themselves are powerful mediators of cytokine induction, anti-apoptosis, cell survival and viral genome maintainence, effective inhibition of COX-2 via well-characterized clinically approved COX-2 inhibitors could potentially be used in treatment to control latent KSHV infection and ameliorate KS.


Zdroje

1. BoshoffC

WeissRA

1998 Kaposi's sarcoma-associated herpesvirus. Adv Cancer Res 75 57 86

2. DupinN

FisherC

KellamP

AriadS

TulliezM

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

3. FidlerIJ

SinghRK

YonedaJ

KumarR

XuL

2000 Critical determinants of neoplastic angiogenesis. Cancer J 6 Suppl 3 S225 236

4. CarmelietP

JainRK

2000 Angiogenesis in cancer and other diseases. Nature 407 249 257

5. VartRJ

NikitenkoLL

LagosD

TrotterMW

CannonM

2007 Kaposi's sarcoma-associated herpesvirus-encoded interleukin-6 and G-protein-coupled receptor regulate angiopoietin-2 expression in lymphatic endothelial cells. Cancer Res 67 4042 4051

6. SadagopanS

Sharma-WaliaN

VeettilMV

BotteroV

LevineR

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

7. McAllisterSC

HansenSG

RuhlRA

RaggoCM

DeFilippisVR

2004 Kaposi sarcoma-associated herpesvirus (KSHV) induces heme oxygenase-1 expression and activity in KSHV-infected endothelial cells. Blood 103 3465 3473

8. Di BartoloDL

CannonM

LiuYF

RenneR

ChadburnA

2008 KSHV LANA inhibits TGF-beta signaling through epigenetic silencing of the TGF-beta type II receptor. Blood 111 4731 4740

9. BoshoffC

WeissRA

1997 Aetiology of Kaposi's sarcoma: current understanding and implications for therapy. Mol Med Today 3 488 494

10. BlackbournDJ

LennetteE

KlenckeB

MosesA

ChandranB

2000 The restricted cellular host range of human herpesvirus 8. Aids 14 1123 1133

11. HaywardGS

2003 Initiation of angiogenic Kaposi's sarcoma lesions. Cancer Cell 3 1 3

12. QianLW

XieJ

YeF

GaoSJ

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

13. RussoJJ

BohenzkyRA

ChienMC

ChenJ

YanM

1996 Nucleotide sequence of the Kaposi sarcoma-associated herpesvirus (HHV8). Proc Natl Acad Sci U S A 93 14862 14867

14. NeipelF

AlbrechtJC

EnsserA

HuangYQ

LiJJ

1997 Human herpesvirus 8 encodes a homolog of interleukin-6. J Virol 71 839 842

15. BaisC

Van GeelenA

ErolesP

MutluA

ChiozziniC

2003 Kaposi's sarcoma associated herpesvirus G protein-coupled receptor immortalizes human endothelial cells by activation of the VEGF receptor-2/ KDR. Cancer Cell 3 131 143

16. AttigaFA

FernandezPM

WeeraratnaAT

ManyakMJ

PatiernoSR

2000 Inhibitors of prostaglandin synthesis inhibit human prostate tumor cell invasiveness and reduce the release of matrix metalloproteinases. Cancer Res 60 4629 4637

17. MoorePS

ChangY

2001 Molecular virology of Kaposi's sarcoma-associated herpesvirus. Philos Trans R Soc Lond B Biol Sci 356 499 516

18. McCormickC

GanemD

2005 The kaposin B protein of KSHV activates the p38/MK2 pathway and stabilizes cytokine mRNAs. Science 307 739 741

19. MurphyPM

1997 Pirated genes in Kaposi's sarcoma. Nature 385 296 297, 299

20. MilliganS

RobinsonM

O'DonnellE

BlackbournDJ

2004 Inflammatory cytokines inhibit Kaposi's sarcoma-associated herpesvirus lytic gene transcription in in vitro-infected endothelial cells. J Virol 78 2591 2596

21. BoshoffC

GaoSJ

HealyLE

MatthewsS

ThomasAJ

1998 Establishing a KSHV+ cell line (BCP-1) from peripheral blood and characterizing its growth in Nod/SCID mice. Blood 91 1671 1679

22. StaskusKA

ZhongW

GebhardK

HerndierB

WangH

1997 Kaposi's sarcoma-associated herpesvirus gene expression in endothelial (spindle) tumor cells. J Virol 71 715 719

23. DittmerD

LagunoffM

RenneR

StaskusK

HaaseA

1998 A cluster of latently expressed genes in Kaposi's sarcoma-associated herpesvirus. J Virol 72 8309 8315

24. McClureLV

SullivanCS

2008 Kaposi's sarcoma herpes virus taps into a host microRNA regulatory network. Cell Host Microbe 3 1 3

25. NaranattPP

KrishnanHH

SvojanovskySR

BloomerC

MathurS

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

26. Sharma-WaliaN

RaghuH

SadagopanS

SivakumarR

VeettilMV

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

27. ShelbyBD

LaMarcaHL

McFerrinHE

NelsonAB

LaskyJA

2007 Kaposi's sarcoma associated herpesvirus G-protein coupled receptor activation of cyclooxygenase-2 in vascular endothelial cells. Virol J 4 87

28. BrinkmannMM

PietrekM

Dittrich-BreiholzO

KrachtM

SchulzTF

2007 Modulation of host gene expression by the K15 protein of Kaposi's sarcoma-associated herpesvirus. J Virol 81 42 58

29. VaneJR

BottingRM

1998 Anti-inflammatory drugs and their mechanism of action. Inflamm Res 47 Suppl 2 S78 87

30. SmithWL

DeWittDL

GaravitoRM

2000 Cyclooxygenases: structural, cellular, and molecular biology. Annu Rev Biochem 69 145 182

31. LinDT

SubbaramaiahK

ShahJP

DannenbergAJ

BoyleJO

2002 Cyclooxygenase-2: a novel molecular target for the prevention and treatment of head and neck cancer. Head Neck 24 792 799

32. DannenbergAJ

SubbaramaiahK

2003 Targeting cyclooxygenase-2 in human neoplasia: rationale and promise. Cancer Cell 4 431 436

33. DempkeW

RieC

GrotheyA

SchmollHJ

2001 Cyclooxygenase-2: a novel target for cancer chemotherapy? J Cancer Res Clin Oncol 127 411 417

34. Sharma-WaliaN

KrishnanHH

NaranattPP

ZengL

SmithMS

2005 ERK1/2 and MEK1/2 induced by Kaposi's sarcoma-associated herpesvirus (human herpesvirus 8) early during infection of target cells are essential for expression of viral genes and for establishment of infection. J Virol 79 10308 10329

35. Sharma-WaliaN

NaranattPP

KrishnanHH

ZengL

ChandranB

2004 Kaposi's sarcoma-associated herpesvirus/human herpesvirus 8 envelope glycoprotein gB induces the integrin-dependent focal adhesion kinase-Src-phosphatidylinositol 3-kinase-rho GTPase signal pathways and cytoskeletal rearrangements. J Virol 78 4207 4223

36. TiscorniaG

SingerO

VermaIM

2006 Design and cloning of lentiviral vectors expressing small interfering RNAs. Nat Protoc 1 234 240

37. SivakumarR

Sharma-WaliaN

RaghuH

VeettilMV

SadagopanS

2008 Kaposi's sarcoma-associated herpesvirus induces sustained levels of vascular endothelial growth factors A and C early during in vitro infection of human microvascular dermal endothelial cells: biological implications. J Virol 82 1759 1776

38. CesarmanE

ChangY

MoorePS

SaidJW

KnowlesDM

1995 Kaposi's sarcoma-associated herpesvirus-like DNA sequences in AIDS-related body-cavity-based lymphomas. N Engl J Med 332 1186 1191

39. GanemD

2006 KSHV infection and the pathogenesis of Kaposi's sarcoma. Annu Rev Pathol 1 273 296

40. CornelissenM

van der KuylAC

van den BurgR

ZorgdragerF

van NoeselCJ

2003 Gene expression profile of AIDS-related Kaposi's sarcoma. BMC Cancer 3 7

41. KrishnanHH

NaranattPP

SmithMS

ZengL

BloomerC

2004 Concurrent expression of latent and a limited number of lytic genes with immune modulation and antiapoptotic function by Kaposi's sarcoma-associated herpesvirus early during infection of primary endothelial and fibroblast cells and subsequent decline of lytic gene expression. J Virol 78 3601 3620

42. AnFQ

FolarinHM

CompitelloN

RothJ

GersonSL

2006 Long-term-infected telomerase-immortalized endothelial cells: a model for Kaposi's sarcoma-associated herpesvirus latency in vitro and in vivo. J Virol 80 4833 4846

43. JiangXH

LamSK

LinMC

JiangSH

KungHF

2002 Novel target for induction of apoptosis by cyclo-oxygenase-2 inhibitor SC-236 through a protein kinase C-beta(1)-dependent pathway. Oncogene 21 6113 6122

44. HeQ

LuoX

JinW

HuangY

ReddyMV

2008 Celecoxib and a novel COX-2 inhibitor ON09310 upregulate death receptor 5 expression via GADD153/CHOP. Oncogene 27 2656 2660

45. von RahdenBH

SteinHJ

PuhringerF

KochI

LangerR

2005 Coexpression of cyclooxygenases (COX-1, COX-2) and vascular endothelial growth factors (VEGF-A, VEGF-C) in esophageal adenocarcinoma. Cancer Res 65 5038 5044

46. VisseR

NagaseH

2003 Matrix metalloproteinases and tissue inhibitors of metalloproteinases: structure, function, and biochemistry. Circ Res 92 827 839

47. OverallCM

KleifeldO

2006 Towards third generation matrix metalloproteinase inhibitors for cancer therapy. Br J Cancer 94 941 946

48. KleinG

VellengaE

FraaijeMW

KampsWA

de BontES

2004 The possible role of matrix metalloproteinase (MMP)-2 and MMP-9 in cancer, e.g. acute leukemia. Crit Rev Oncol Hematol 50 87 100

49. PantanowitzL

DezubeBJ

Hernandez-BarrantesS

TahanSR

DabbousMK

2006 Matrix metalloproteinases in the progression and regression of Kaposi's sarcoma. J Cutan Pathol 33 793 798

50. RidleyAJ

2001 Rho GTPases and cell migration. J Cell Sci 114 2713 2722

51. BurridgeK

WennerbergK

2004 Rho and Rac take center stage. Cell 116 167 179

52. VeettilMV

Sharma-WaliaN

SadagopanS

RaghuH

SivakumarR

2006 RhoA-GTPase facilitates entry of Kaposi's sarcoma-associated herpesvirus into adherent target cells in a Src-dependent manner. J Virol 80 11432 11446

53. DormondO

BezziM

MariottiA

RueggC

2002 Prostaglandin E2 promotes integrin alpha Vbeta 3-dependent endothelial cell adhesion, rac-activation, and spreading through cAMP/PKA-dependent signaling. J Biol Chem 277 45838 45846

54. ErkanliS

BolatF

KayaselcukF

DemirhanB

KuscuE

2007 COX-2 and survivin are overexpressed and positively correlated in endometrial carcinoma. Gynecol Oncol 104 320 325

55. BaopingY

GuoyongH

JiepingY

ZongxueR

HeshengL

2004 Cyclooxygenase-2 inhibitor nimesulide suppresses telomerase activity by blocking Akt/PKB activation in gastric cancer cell line. Dig Dis Sci 49 948 953

56. SadagopanS

Sharma-WaliaN

VeettilMV

RaghuH

SivakumarR

2007 Kaposi's sarcoma-associated herpesvirus induces sustained NF-kappaB activation during de novo infection of primary human dermal microvascular endothelial cells that is essential for viral gene expression. J Virol 81 3949 3968

57. AmbrusJL

StollHL

KleinEA

KarakousisCP

StadlerS

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

58. RossielloL

RuoccoE

SignorielloG

MicheliP

RienzoM

2007 Evidence of COX-1 and COX-2 expression in Kaposi's sarcoma tissues. Eur J Cancer 43 1232 1241

59. GalloO

FranchiA

MagnelliL

SardiI

VannacciA

2001 Cyclooxygenase-2 pathway correlates with VEGF expression in head and neck cancer. Implications for tumor angiogenesis and metastasis. Neoplasia 3 53 61

60. HongYK

ForemanK

ShinJW

HirakawaS

CurryCL

2004 Lymphatic reprogramming of blood vascular endothelium by Kaposi sarcoma-associated herpesvirus. Nat Genet 36 683 685

61. GrogerM

LoeweR

HolnthonerW

EmbacherR

PillingerM

2004 IL-3 induces expression of lymphatic markers Prox-1 and podoplanin in human endothelial cells. J Immunol 173 7161 7169

62. InoueH

TakamoriM

ShimoyamaY

IshibashiH

YamamotoS

2002 Regulation by PGE2 of the production of interleukin-6, macrophage colony stimulating factor, and vascular endothelial growth factor in human synovial fibroblasts. Br J Pharmacol 136 287 295

63. WangD

MannJR

DuBoisRN

2005 The role of prostaglandins and other eicosanoids in the gastrointestinal tract. Gastroenterology 128 1445 1461

64. LeeDC

ChuaDT

WeiWI

ShamJS

LauAS

2007 Induction of matrix metalloproteinases by Epstein-Barr virus latent membrane protein 1 isolated from nasopharyngeal carcinoma. Biomed Pharmacother 61 520 526

65. TakeshitaH

YoshizakiT

MillerWE

SatoH

FurukawaM

1999 Matrix metalloproteinase 9 expression is induced by Epstein-Barr virus latent membrane protein 1 C-terminal activation regions 1 and 2. J Virol 73 5548 5555

66. LuJ

ChuaHH

ChenSY

ChenJY

TsaiCH

2003 Regulation of matrix metalloproteinase-1 by Epstein-Barr virus proteins. Cancer Res 63 256 262

67. ChungTW

MoonSK

LeeYC

KimJG

KoJH

2002 Enhanced expression of matrix metalloproteinase-9 by hepatitis B virus infection in liver cells. Arch Biochem Biophys 408 147 154

68. MastroianniCM

LiuzziGM

2007 Matrix metalloproteinase dysregulation in HIV infection: implications for therapeutic strategies. Trends Mol Med 13 449 459

69. CaoR

ErikssonA

KuboH

AlitaloK

CaoY

2004 Comparative evaluation of FGF-2-, VEGF-A-, and VEGF-C-induced angiogenesis, lymphangiogenesis, vascular fenestrations, and permeability. Circ Res 94 664 670

70. KoskivirtaI

RahkonenO

MayranpaaM

PakkanenS

HusheemM

2006 Tissue inhibitor of metalloproteinases 4 (TIMP4) is involved in inflammatory processes of human cardiovascular pathology. Histochem Cell Biol 126 335 342

71. ChircoR

LiuXW

JungKK

KimHR

2006 Novel functions of TIMPs in cell signaling. Cancer Metastasis Rev 25 99 113

72. YaoL

SalvucciO

CardonesAR

HwangST

AokiY

2003 Selective expression of stromal-derived factor-1 in the capillary vascular endothelium plays a role in Kaposi sarcoma pathogenesis. Blood 102 3900 3905

73. FujimuroM

WuFY

ApRhysC

KajumbulaH

YoungDB

2003 A novel viral mechanism for dysregulation of beta-catenin in Kaposi's sarcoma-associated herpesvirus latency. Nat Med 9 300 306

74. OttingerM

ChristallaT

NathanK

BrinkmannMM

Viejo-BorbollaA

2006 Kaposi's sarcoma-associated herpesvirus LANA-1 interacts with the short variant of BRD4 and releases cells from a BRD4- and BRD2/RING3-induced G1 cell cycle arrest. J Virol 80 10772 10786

75. LimK

HanC

XuL

IsseK

DemetrisAJ

2008 Cyclooxygenase-2-derived prostaglandin E2 activates beta-catenin in human cholangiocarcinoma cells: evidence for inhibition of these signaling pathways by omega 3 polyunsaturated fatty acids. Cancer Res 68 553 560

76. SawasdikosolS

PyarajanS

AlzabinS

MatejovicG

BurakoffSJ

2007 Prostaglandin E2 activates HPK1 kinase activity via a PKA-dependent pathway. J Biol Chem 282 34693 34699

77. PhamL

BezouglaiaO

CamargoPM

NervinaJM

TetradisS

2007 Prostanoids induce egr1 gene expression in cementoblastic OCCM cells. J Periodontal Res 42 486 493

78. FriasMA

RebsamenMC

Gerber-WichtC

LangU

2007 Prostaglandin E2 activates Stat3 in neonatal rat ventricular cardiomyocytes: A role in cardiac hypertrophy. Cardiovasc Res 73 57 65

79. BuchananFG

DuBoisRN

2006 Connecting COX-2 and Wnt in cancer. Cancer Cell 9 6 8

80. KrysanK

ReckampKL

DalwadiH

SharmaS

RozengurtE

2005 Prostaglandin E2 activates mitogen-activated protein kinase/Erk pathway signaling and cell proliferation in non-small cell lung cancer cells in an epidermal growth factor receptor-independent manner. Cancer Res 65 6275 6281

81. YamakiT

EndohK

MiyaharaM

NagamineI

Thi Thu HuongN

2004 Prostaglandin E2 activates Src signaling in lung adenocarcinoma cell via EP3. Cancer Lett 214 115 120

82. Mochizuki-OdaN

MoriK

NegishiM

ItoS

1991 Prostaglandin E2 activates Ca2+ channels in bovine adrenal chromaffin cells. J Neurochem 56 541 547

83. MicaliA

MediciN

SottileA

VenzaM

VenzaI

1996 Prostaglandin E2 induction of binding activity to CRE and AP-2 elements in human T lymphocytes. Cell Immunol 174 99 105

84. LiuXH

KirschenbaumA

LuM

YaoS

DosoretzA

2002 Prostaglandin E2 induces hypoxia-inducible factor-1alpha stabilization and nuclear localization in a human prostate cancer cell line. J Biol Chem 277 50081 50086

85. WangX

KleinRD

2007 Prostaglandin E2 induces vascular endothelial growth factor secretion in prostate cancer cells through EP2 receptor-mediated cAMP pathway. Mol Carcinog 46 912 923

86. ItoH

DuxburyM

BenoitE

ClancyTE

ZinnerMJ

2004 Prostaglandin E2 enhances pancreatic cancer invasiveness through an Ets-1-dependent induction of matrix metalloproteinase-2. Cancer Res 64 7439 7446

87. BradburyD

ClarkeD

SeedhouseC

CorbettL

StocksJ

2005 Vascular endothelial growth factor induction by prostaglandin E2 in human airway smooth muscle cells is mediated by E prostanoid EP2/EP4 receptors and SP-1 transcription factor binding sites. J Biol Chem 280 29993 30000

88. ChuangPC

SunHS

ChenTM

TsaiSJ

2006 Prostaglandin E2 induces fibroblast growth factor 9 via EP3-dependent protein kinase Cdelta and Elk-1 signaling. Mol Cell Biol 26 8281 8292

89. GeorgeRJ

SturmoskiMA

AnantS

HouchenCW

2007 EP4 mediates PGE2 dependent cell survival through the PI3 kinase/AKT pathway. Prostaglandins Other Lipid Mediat 83 112 120

90. YeFC

ZhouFC

XieJP

KangT

GreeneW

2008 Kaposi's sarcoma-associated herpesvirus latent gene vFLIP inhibits viral lytic replication through NF-kappaB-mediated suppression of the AP-1 pathway: a novel mechanism of virus control of latency. J Virol 82 4235 4249

91. CaiQ

LanK

VermaSC

SiH

LinD

2006 Kaposi's sarcoma-associated herpesvirus latent protein LANA interacts with HIF-1 alpha to upregulate RTA expression during hypoxia: Latency control under low oxygen conditions. J Virol 80 7965 7975

92. LanK

KuppersDA

RobertsonES

2005 Kaposi's sarcoma-associated herpesvirus reactivation is regulated by interaction of latency-associated nuclear antigen with recombination signal sequence-binding protein Jkappa, the major downstream effector of the Notch signaling pathway. J Virol 79 3468 3478

93. DeWittDL

1999 Cox-2-selective inhibitors: the new super aspirins. Mol Pharmacol 55 625 631

94. SunQ

LiuQ

ZhengY

CaoX

2008 Rapamycin suppresses TLR4-triggered IL-6 and PGE(2) production of colon cancer cells by inhibiting TLR4 expression and NF-kappaB activation. Mol Immunol 45 2929 2936

95. ManningDS

SheehanKM

ByrneMF

KayEW

MurrayFE

2007 Cyclooxygenase-2 expression in chronic hepatitis C and the effect of interferon alpha treatment. J Gastroenterol Hepatol 22 1633 1637

96. DuffM

StapletonPP

MestreJR

MaddaliS

SmythGP

2003 Cyclooxygenase-2 inhibition improves macrophage function in melanoma and increases the antineoplastic activity of interferon gamma. Ann Surg Oncol 10 305 313

97. NakanishiY

KamijoR

TakizawaK

HatoriM

NagumoM

2001 Inhibitors of cyclooxygenase-2 (COX-2) suppressed the proliferation and differentiation of human leukaemia cell lines. Eur J Cancer 37 1570 1578

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