Trichosanthin inhibits antigen-specific T cell expansion through nitric oxide-mediated apoptosis pathway.
Trichosanthin (TCS) has been found to exhibit inflammation-suppressing effect but the underlying mechanisms are not clear. In this study, we found that TCS inhibited OVA-specific T cell proliferation in a dose-dependent manner. Such inhibition was correlated with enhanced cell death. At the same time, inducible nitric oxide synthase (iNOS) mRNA expression and protein levels were found increased in cells treated with TCS, and nitric oxide (NO) production by cells was elevated in the presence of TCS. When L-NIL, the specific inhibitor of iNOS, was added to suppress NO production induced by TCS, OVA-specific cell death was significantly inhibited, meanwhile, thymidine incorporation of cells was rescued towards normal levels. These results indicate that TCS could inhibit antigen-specific T cell activation via NO-mediated apoptosis pathway.
Li
Fang
F
Joint Immunology Laboratory of Institute of Health Sciences and Shanghai Institute of Immunology, Shanghai Institutes for Biological Sciences/Chinese Academy of Sciences, and Shanghai Second Medical University, Shanghai 200025, China.
Mei
Yunhua
Y
Wang
Ying
Y
Chen
Chunhua
C
Tu
Jianglong
J
Xiao
Baoguo
B
Xu
Lingyun
L
D000818:Animals; D000941:Antigens / Q000276:immunology*; D017209:Apoptosis / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D006836:Hydro-Lyases / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D010047:Ovalbumin / Q000494:pharmacology; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D015978:Trichosanthin / Q000494:pharmacology*
D000941:Antigens; D009569:Nitric Oxide; D015978:Trichosanthin; D010047:Ovalbumin; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; D006836:Hydro-Lyases; C045581:lactate dehydratase