Effects of esculentoside A on autoimmune syndrome induced by Campylobacterjejuni in mice and its modulation on T-lymphocyte proliferation and apoptosis.
Esculentoside A (EsA), a saponin isolated from the root of Phytolacca esculenta, has been reported to exert anti-inflammatory effects in several animal models of acute and chronic inflammation by inhibiting the production and activity of pro-inflammatory cytokines in macrophages and epithelial cells. However, little is known about its modulation on T cells. In the present study, we further investigated its potential in treatment of autoimmune disease and its modulation on T cells, using an experimental autoimmune model established through immunizing mice with Campylobacterjejuni strain CJ-S(131) in Freund's complete adjuvant. Our results demonstrated that EsA administration markedly alleviated the inflammatory injury in liver and kidney of model mice, decreased the anti-CD3/CD28-stimulated proliferation of splenocytes and lymph node cells, and reduced the percentage of CD3+, CD4+, and CD8+ lymphocytes in peripheral blood. Furthermore, we demonstrated that EsA induced apoptosis in ConA-activated thymocytes but not in non-activated thymocytes. Gene expression analysis revealed that EsA up-regulated the expression of a group of pro-apoptotic genes more profoundly in Con A-activated thymocytes than in non-activated thymocytes. EsA-affected pro-apoptotic genes included those involved in Fas induction, p53 activation, redox metabolism, calcium- and glucocorticoid-induced apoptosis signals, suggesting that EsA may modulate multiple apoptotic signal pathways in activated T cells. Taken together, our findings suggest that EsA may be useful for the treatment of autoimmune disease through modulation on T cell-mediated adaptive immunity.
Hu
Zhenlin
Z
Department of Biochemical Pharmacy, School of Pharmacy, Second Military Medical University, Shanghai, China.
Qiu
Lei
L
Xiao
Zhenyu
Z
Wang
Jing
J
Yu
Qi
Q
Li
Jianzhong
J
Feng
Hao
H
Guo
Cheng
C
Zhang
Junping
J
D000818:Animals; D015703:Antigens, CD / Q000096:biosynthesis; D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics / Q000276:immunology; D051017:Apoptosis Regulatory Proteins / Q000096:biosynthesis / Q000235:genetics; D001327:Autoimmune Diseases / Q000188:drug therapy* / Q000276:immunology; D016123:Campylobacter jejuni / Q000276:immunology*; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects*; D004195:Disease Models, Animal; D056747:Immunomodulation; D007668:Kidney / Q000187:drug effects / Q000276:immunology; D008099:Liver / Q000187:drug effects / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009828:Oleanolic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D029603:Phytolacca / Q000276:immunology; D012503:Saponins / Q000494:pharmacology* / Q000627:therapeutic use; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000473:pathology
D015703:Antigens, CD; D051017:Apoptosis Regulatory Proteins; D012503:Saponins; C076297:esculentoside A; D009828:Oleanolic Acid