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KMID : 0620920070390060715
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Experimental & Molecular Medicine
2007 Volume.39 No. 6 p.715 ~ p.721
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lastrol inhibits production of nitric oxideandproinflammatory cytokines through MAPK signal transduction and NF-kB in LPS-stimulated BV-2 microglial cells
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Jung Hyo-Won
Chung Yoo-Sun
Kim Yoon-Seong
Park Yong-Ki
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Abstract
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Excessive production of nitric oxide (NO) and proinflammatory cytokines from activated microglia play an important role in human neurodegenerative disorders. Here, we investigated whether celastrol, which has been used as a potent anti-inflammatory and anti-oxidative agent in Chinese medicine, attenuates excessive production of NO and proinflammatory cytokines such as TNF-a and IL-1b in LPS-stimulated BV-2 cells, a mouse microglial cell line. We report here that the LPS-elicited excessive production of NO, TNF-a, and IL-1b in BV-2 cells was largely inhibited in the presence of celastrol, and the attenuation of inducible iNOS and these cytokines resulted from the reduced expression of mRNAs of iNOS and these cytokines, respectively. The molecular mechanisms that underlie celastrol-mediated attenuation were the inhibition of LPS-induced phosphorylation of MAPK/ERK1/2 and the DNA binding activity of NF-kB in BV-2 cells. The results indicate that celastrol effectively attenuated NO and proinflammatory cytokine production via the inhibition of ERK1/2 phosphorylation and NF-kB activation in LPS-activated microglia. Thus, celastrol may be an effective therapeutic candidate for use in the treatment of neurodegenerative human brain disorders.
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KEYWORD
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anti-inflammatory agents, cytokines, extracellular signal-regulated MAP kinases, medicine, Chinese traditional, microglia, nitric oxide synthase type II, triterpene
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