title: Celastrol suppresses morphological and transcriptional responses in microglial cells upon stimulation with double-stranded RNA.
abstract: Despite the pivotal role of microglia in the immune system of the brain, a growing body of evidence suggests that excessive microglial activation provokes neuronal and glial damage, leading to neurodegenerative and neuroinflammatory disorders. Celastrol, a triterpene, is a potent anti-inflammatory and antioxidant compound derived from perennial creeping plants belonging to the Celastraceae family. In the current study, we have analyzed the effect of celastrol on morphological and transcriptional responses in microglial MG6 cells upon stimulation with double-stranded RNA, a strong activator of innate immune cells. In the presence of celastrol, morphological changes were inhibited in double-stranded RNA-stimulated microglia. It was also found that the treatment of microglia with celastrol led to a significant decrease in the double-stranded RNA-induced expression of proinflammatory cytokines and chemokines. These data demonstrate that celastrol inhibits morphological and transcriptional responses during microglial activation.
authors.affiliation: Laboratory of Neurovirology, Department of Virology 1, National Institute of Infectious Diseases, Shinjuku, Tokyo, Japan. nakamich@nih.go.jp
authors.forename: Kazuo
authors.initials: K
authors.lastname: Nakamichi
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kitani
authors.forename: Mutsuyo
authors.initials: M
authors.lastname: Takayama-Ito
authors.forename: Kinjiro
authors.initials: K
authors.lastname: Morimoto
authors.forename: Ichiro
authors.initials: I
authors.lastname: Kurane
authors.forename: Masayuki
authors.initials: M
authors.lastname: Saijo
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D002461:Cell Line, Transformed; D048429:Cell Size / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D016207:Cytokines / Q000378:metabolism; D003599:Cytoskeleton / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D053263:Gene Regulatory Networks / Q000187:drug effects*; D007369:Interferon Inducers / Q000494:pharmacology; D051379:Mice; D017628:Microglia / Q000166:cytology* / Q000187:drug effects*; D053978:Pentacyclic Triterpenes; D011070:Poly I-C / Q000494:pharmacology; D013997:Time Factors; D014315:Triterpenes / Q000494:pharmacology*
chemical_list: D000199:Actins; D016207:Cytokines; D007369:Interferon Inducers; D053978:Pentacyclic Triterpenes; D014315:Triterpenes; C050414:celastrol; D011070:Poly I-C