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Inhibition of inducible NO synthase, cyclooxygenase-2 and interleukin-1beta by torilin is mediated by mitogen-activated protein kinases in microglial BV2 cells.
Br J Pharmacol. 2009 Mar; 156(6):933-40.BJ

Abstract

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-1beta (IL-1beta) 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-kappaB (NF-kappaB) and cyclic AMP-responsive element (CRE)-binding protein (CREB).

KEY RESULTS

Torilin significantly reduced the LPS-induced expression of iNOS, COX-2 and IL-1beta, and the subsequent release of NO, prostaglandin E(2) and IL-1beta 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-kappaB and CREB was shown by torilin-mediated recovery of LPS-induced degradation of inhibitor kappaB-alpha 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-1beta via down-regulation of ERK1/2, p38 MAPK, NF-kappaB and CREB and suggests that torilin has a potential as an anti-inflammatory drug candidate.

Authors+Show Affiliations

College of Pharmacy and Research Institute of Pharmaceutical Science, Seoul National University, Seoul, Korea.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

19298258

Citation

Choi, Y, et al. "Inhibition of Inducible NO Synthase, Cyclooxygenase-2 and Interleukin-1beta By Torilin Is Mediated By Mitogen-activated Protein Kinases in Microglial BV2 Cells." British Journal of Pharmacology, vol. 156, no. 6, 2009, pp. 933-40.
Choi Y, Lee MK, Lim SY, et al. Inhibition of inducible NO synthase, cyclooxygenase-2 and interleukin-1beta by torilin is mediated by mitogen-activated protein kinases in microglial BV2 cells. Br J Pharmacol. 2009;156(6):933-40.
Choi, Y., Lee, M. K., Lim, S. Y., Sung, S. H., & Kim, Y. C. (2009). Inhibition of inducible NO synthase, cyclooxygenase-2 and interleukin-1beta by torilin is mediated by mitogen-activated protein kinases in microglial BV2 cells. British Journal of Pharmacology, 156(6), 933-40. https://doi.org/10.1111/j.1476-5381.2009.00022.x
Choi Y, et al. Inhibition of Inducible NO Synthase, Cyclooxygenase-2 and Interleukin-1beta By Torilin Is Mediated By Mitogen-activated Protein Kinases in Microglial BV2 Cells. Br J Pharmacol. 2009;156(6):933-40. PubMed PMID: 19298258.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Inhibition of inducible NO synthase, cyclooxygenase-2 and interleukin-1beta by torilin is mediated by mitogen-activated protein kinases in microglial BV2 cells. AU - Choi,Y, AU - Lee,M K, AU - Lim,S Y, AU - Sung,S H, AU - Kim,Y C, PY - 2009/3/21/entrez PY - 2009/3/21/pubmed PY - 2009/7/21/medline SP - 933 EP - 40 JF - British journal of pharmacology JO - Br J Pharmacol VL - 156 IS - 6 N2 - 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-1beta (IL-1beta) 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-kappaB (NF-kappaB) and cyclic AMP-responsive element (CRE)-binding protein (CREB). KEY RESULTS: Torilin significantly reduced the LPS-induced expression of iNOS, COX-2 and IL-1beta, and the subsequent release of NO, prostaglandin E(2) and IL-1beta 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-kappaB and CREB was shown by torilin-mediated recovery of LPS-induced degradation of inhibitor kappaB-alpha 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-1beta via down-regulation of ERK1/2, p38 MAPK, NF-kappaB and CREB and suggests that torilin has a potential as an anti-inflammatory drug candidate. SN - 1476-5381 UR - https://www.unboundmedicine.com/medline/citation/19298258/Inhibition_of_inducible_NO_synthase_cyclooxygenase_2_and_interleukin_1beta_by_torilin_is_mediated_by_mitogen_activated_protein_kinases_in_microglial_BV2_cells_ L2 - https://doi.org/10.1111/j.1476-5381.2009.00022.x DB - PRIME DP - Unbound Medicine ER -