title: Triptolide inhibits B7-H1 expression on proinflammatory factor activated renal tubular epithelial cells by decreasing NF-kappaB transcription.
abstract: Triptolide has been used extensively in China for the treatment of autoimmune diseases and tumor for many centuries. Nevertheless, little is known about its exact immunosuppressive and anti-inflammatory properties. Increasing recognition of the importance of renal tubular epithelial cells (TECs) in renal diseases raises the question whether triptolide can regulate TEC activity. In this study, various cultured human and murine TECs were exposed to tumor necrotic factor-alpha (TNF-alpha) and triptolide, followed to examine the expression of B7-H1 and B7-DC. Flow cytometric analysis revealed that B7-H1 but not B7-DC constitutively expresses on TECs, and the B7-H1 protein expression was profoundly up-regulated by the stimulation of TNF-alpha with a dose-dependent manner. However, triptolide under non-cytotoxic concentration could down-regulate B7-H1 expression on activated TECs at both mRNA and protein level. This effect was transcription factor NF-kappaB dependent. Interestingly, the significant damping effect of triptolide on B7-H1 signal could promote interleukin-2 production by T cell hybridoma (C10) after antigen presentation and enhance cytokine (IFN-gamma and IL-2) secretion by anti-CD3 activated T cells. Our results indicated that triptolide could regulate TEC activity via B7-H1, in addition to previously reported it directly affects the production of some inflammatory factors by T cells, tumor cells and peripheral blood mononuclear cells.
authors.affiliation: Institute of Immunology, PLA, The Third Military Medical University, Chongqing 400038, PR China.
authors.forename: Yongwen
authors.initials: Y
authors.lastname: Chen
authors.forename: Jingbo
authors.initials: J
authors.lastname: Zhang
authors.forename: Jingyi
authors.initials: J
authors.lastname: Li
authors.forename: Tingting
authors.initials: T
authors.lastname: Zhao
authors.forename: Liyun
authors.initials: L
authors.lastname: Zou
authors.forename: Yan
authors.initials: Y
authors.lastname: Tang
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Zhang
authors.forename: Yuzhang
authors.initials: Y
authors.lastname: Wu
mesh_terms: D000818:Animals; D017951:Antigen Presentation / Q000276:immunology; D015703:Antigens, CD; D018122:B7-1 Antigen / Q000235:genetics*; D060890:B7-H1 Antigen; D018920:Coculture Techniques; D016572:Cyclosporine / Q000494:pharmacology; D016207:Cytokines / Q000096:biosynthesis; D003602:Cytotoxicity, Immunologic; D004224:Diterpenes / Q000737:chemistry / Q000494:pharmacology*; D015536:Down-Regulation / Q000187:drug effects*; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism; D004852:Epoxy Compounds; D006801:Humans; D006825:Hybridomas; D007166:Immunosuppressive Agents; D018836:Inflammation Mediators / Q000737:chemistry / Q000494:pharmacology*; D007684:Kidney Tubules / Q000166:cytology*; D008562:Membrane Glycoproteins / Q000235:genetics*; D051379:Mice; D008807:Mice, Inbred BALB C; D016328:NF-kappa B / Q000235:genetics*; D010455:Peptides / Q000235:genetics*; D010616:Phenanthrenes / Q000737:chemistry / Q000494:pharmacology*; D061027:Programmed Cell Death 1 Ligand 2 Protein; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013601:T-Lymphocytes / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D015703:Antigens, CD; D018122:B7-1 Antigen; D060890:B7-H1 Antigen; C423236:CD274 protein, human; D016207:Cytokines; D004224:Diterpenes; D004852:Epoxy Compounds; D007166:Immunosuppressive Agents; D018836:Inflammation Mediators; D008562:Membrane Glycoproteins; D016328:NF-kappa B; C556977:PDCD1LG2 protein, human; C556978:Pdcd1lg2 protein, mouse; D010455:Peptides; D010616:Phenanthrenes; D061027:Programmed Cell Death 1 Ligand 2 Protein; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; C001899:triptolide; D016572:Cyclosporine