Sinomenine inhibits B7-H1 and B7-DC expression on human renal tubular epithelial cells.
Previous studies have shown that sinomenine possesses potent immunoregulatory properties. However, little is known about its exact mechanisms of action. Increasing recognition of the importance of renal tubular epithelial cells (TECs) in renal diseases raises the question whether sinomenine can regulate TEC activity. In this study, cultured human TECs were exposed to proinflammatory factors interferon-gamma (IFN-gamma) and tumor necrotic factor-alpha (TNF-alpha) in presence or absence of sinomenine for 72 h, followed by analysis of surface expression of costimulatory molecules. Flow cytometric analysis revealed that various costimulatory molecules were expressed on TECs and that they were significantly up-regulated by the simulation of IFN-gamma and TNF-alpha. However, sinomenine especially down-regulated B7-H1 and B7-DC expression on TECs at both mRNA and protein levels. Moreover, the significant damping effect of sinomenine on B7-H1 and B7-DC signals could promote IL-2 and IFN-gamma production by co-cultured CD4(+) T cell. Our results indicated that sinomenine could regulate TECs activity via B7-H1 and B7-DC, in addition to previously reported its effects on some pro-inflammatory factors production by macrophages and peripheral blood mononuclear cells.
Chen
Yongwen
Y
Institute of Immunology of PLA, Third Military Medical University, Chongqing 400038, P.R. China.
Li
Jingyi
J
Zhang
Jingbo
J
Zhao
Tingting
T
Zou
Liyun
L
Tang
Yan
Y
Zhang
Xiaoping
X
Wu
Yuzhang
Y
D015703:Antigens, CD; D018122:B7-1 Antigen / Q000378:metabolism*; D060890:B7-H1 Antigen; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D002460:Cell Line; D002478:Cells, Cultured; D016572:Cyclosporine / Q000494:pharmacology; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007155:Immunologic Factors / Q000494:pharmacology*; D007371:Interferon-gamma / Q000378:metabolism / Q000494:pharmacology; D007376:Interleukin-2 / Q000378:metabolism; D007684:Kidney Tubules / Q000166:cytology / Q000187:drug effects*; D008562:Membrane Glycoproteins / Q000378:metabolism*; D009019:Morphinans / Q000494:pharmacology*; D010455:Peptides / Q000378:metabolism*; D061027:Programmed Cell Death 1 Ligand 2 Protein; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D015703:Antigens, CD; D018122:B7-1 Antigen; D060890:B7-H1 Antigen; C423236:CD274 protein, human; D007155:Immunologic Factors; D007376:Interleukin-2; D008562:Membrane Glycoproteins; D009019:Morphinans; C556977:PDCD1LG2 protein, human; D010455:Peptides; D061027:Programmed Cell Death 1 Ligand 2 Protein; D014409:Tumor Necrosis Factor-alpha; C009271:sinomenine; D007371:Interferon-gamma; D016572:Cyclosporine