Inhibition of inducible NO synthase, cyclooxygenase‐2 and interleukin‐1β by torilin is mediated by mitogen‐activated protein kinases in microglial BV2 cells

British Journal of Pharmacology - Tập 156 Số 6 - Trang 933-940 - 2009
Yoon‐Jung Choi1, Michael K. Lee1, Sun‐Young Lim1, SH Sung1, YC Kim1
1College of Pharmacy and Research Institute of Pharmaceutical Science, Seoul National University, Seoul, Korea

Tóm tắt

Background and purpose:  Traditionally, the stem and root bark of Ulmus davidiana var. japonica (Ulmaceae) have been known to be anti‐inflammatory in Korea. Anti‐inflammatory effects of torilin, isolated from this plant and the underlying mechanisms were examined by using lipopolysaccharide (LPS)‐stimulated microglial BV2 cells.Experimental approach:  The cells were treated with torilin prior to LPS exposure and the effects on pro‐inflammatory enzymes, inducible nitric oxide synthase (iNOS) and cyclooxygenase‐2 (COX‐2), and a pro‐inflammatory cytokine, interleukin‐1β (IL‐1β) were analysed by RT‐PCR, Western blot or elisa. To reveal the mechanism of action of torilin we investigated the involvement of mitogen‐activated protein kinase (MAPK) cascades and their downstream transcription factors, nuclear factor‐κB (NF‐κB) and cyclic AMP‐responsive element (CRE)‐binding protein (CREB).Key results:  Torilin significantly reduced the LPS‐induced expression of iNOS, COX‐2 and IL‐1β, and the subsequent release of NO, prostaglandin E2 and IL‐1β into culture medium. LPS stimulation of extracellular signal‐regulated kinase 1/2 (ERK1/2) and p38 MAPK was inhibited by torilin. In addition, the inhibitory effect of torilin on NF‐κB and CREB was shown by torilin‐mediated recovery of LPS‐induced degradation of inhibitor κB‐α and suppression of LPS‐induced phosphorylation of CREB respectively.Conclusion and implications:  This study indicates that torilin inhibited LPS‐induced iNOS, COX‐2 and IL‐1β via down‐regulation of ERK1/2, p38 MAPK, NF‐κB and CREB and suggests that torilin has a potential as an anti‐inflammatory drug candidate.

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Thông tin xuất bản

British Journal of Pharmacology

Tập 156 Số 6

933-940

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