Pseudolaric acid B suppresses T lymphocyte activation through inhibition of NF-kappaB signaling pathway and p38 phosphorylation.
Pseudolaric acid B (PAB) is a major bioactive component of the medicinal plant Pseudolarix kaempferi. Traditional medicine practitioners in Asia have been using the roots of this plant to treat inflammatory and microbial skin diseases for centuries. In the current study, in vitro immunosuppressive effect of PAB and the underlying mechanisms have been investigated. The results showed that PAB dose-dependently suppressed human T lymphocyte proliferation, IL-2 production and CD25 expression induced by co-stimulation of PMA plus ionomycin or of anti-OKT-3 plus anti-CD28. Mechanistic studies showed that PAB significantly inhibited nuclear translocation of NF-kappaB p65 and phosphorylation and degradation of IkappaB-alpha evoked by co-stimulation of PMA plus ionomycin. PAB could also suppress the phosphorylation of p38 in the MAPKs pathway. Based on these evidences, we conclude that PAB suppressed T lymphocyte activation through inhibition of NF-kappaB and p38 signaling pathways; this would make PAB a strong candidate for further study as an anti-inflammatory agent.
Li
Ting
T
School of Chinese Medicine, Hong Kong Baptist University, 7 Baptist University Road, Kowloon, Hong Kong, China.
Wong
Vincent Kam Wai
VK
Yi
Xiao Qin
XQ
Wong
Yuen Fan
YF
Zhou
Hua
H
Liu
Liang
L
D049109:Cell Proliferation; D004224:Diterpenes / Q000494:pharmacology*; D006801:Humans; D007376:Interleukin-2 / Q000378:metabolism; D053645:Interleukin-2 Receptor alpha Subunit / Q000378:metabolism; D008213:Lymphocyte Activation / Q000187:drug effects*; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects*; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
D004224:Diterpenes; D007376:Interleukin-2; D053645:Interleukin-2 Receptor alpha Subunit; D016328:NF-kappa B; C058391:pseudolaric acid B; D048051:p38 Mitogen-Activated Protein Kinases