Celastrol inhibits production of nitric oxideandproinflammatory cytokines through MAPK signal transduction and NF-kappaB in LPS-stimulated BV-2 microglial cells.
- Author:
Hyo Won JUNG
1
;
Yoo Sun CHUNG
;
Yoon Seong KIM
;
Yong Ki PARK
Author Information
1. Department of Herbology, College of Oriental Medicine, Dongguk University, Gyeongju 780-714, Korea. yongki@dongguk.ac.kr
- Publication Type:Original Article ; Research Support, Non-U.S. Gov't
- Keywords:
anti-inflammatory agents;
cytokines;
extracellular signal-regulated MAP kinases;
medicine, Chinese traditional;
microglia;
nitric oxide synthase type II;
triterpene
- MeSH:
Animals;
Cell Line;
Cytokines/*biosynthesis/drug effects;
Gene Expression Regulation, Enzymologic/drug effects/immunology;
Inflammation/immunology;
Inflammation Mediators/immunology;
Mice;
Microglia/*drug effects/immunology;
Mitogen-Activated Protein Kinases/*physiology;
NF-kappa B/metabolism/*physiology;
Nitric Oxide/*metabolism;
Nitric Oxide Synthase Type II/biosynthesis/drug effects;
RNA, Messenger/analysis;
Signal Transduction/*drug effects/physiology;
Transcription, Genetic/drug effects/immunology;
Triterpenes/*pharmacology
- From:Experimental & Molecular Medicine
2007;39(6):715-721
- CountryRepublic of Korea
- Language:English
-
Abstract:
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-alpha and IL-1beta in LPS-stimulated BV-2 cells, a mouse microglial cell line. We report here that the LPS-elicited excessive production of NO, TNF-alpha, and IL-1beta 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-kappaB 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-kappaB activation in LPS-activated microglia. Thus, celastrol may be an effective therapeutic candidate for use in the treatment of neurodegenerative human brain disorders.
