Celastrol inhibits production of nitric oxide and proinflammatorycytokines through MAPK signal transduction and NF-κB inLPS-stimulated BV-2 microglial cells

• Published in: Experimental & molecular medicine 2007, 39(6), , pp.715-721
• Main Authors: Hyo Won Jung, Yoo Sun Chung, Yoon Seong Kim, 박용기
• Format: Article
• Language: Korean
• Subjects: 생화학
• ISSN: 1226-3613; 2092-6413

Excessive production of nitric oxide (NO) and proin-flammatory cytokines from activated microglia play an Here, we investigated whether celastrol, which has been used as a potent anti-inflammatory and anti-oxi-dative agent in Chinese medicine, attenuates ex-cessive production of NO and proinflammatory cyto-kines such as TNF-α and IL-1β in LPS-stimulated BV-2 cells, a mouse microglial cell line. We report here that the LPS-elicited excessive production of NO, TNF-α, and IL-1βence of celastrol, and the attenuation of inducible iNOS and these cytokines resulted from the reduced ex-pression of mRNAs of iNOS and these cytokines, respectively. The molecular mechanisms that underlie celastrol-mediated atenuation were the inhibition of LPS-induced phosphorylation of MAPK/ERK1/2 and the DNA binding activity of NF-κB in BV-2 cells. The results indicate that celastrol effectively attenuated inhibition of ERK1/2 phosphorylation and NF-κB ac-tivation in LPS-activated microglia. Thus, celastrol may be an effective therapeutic candidate for use in the treatment of neurodegenerative human brain disorders. KCI Citation Count: 79