title: Anti-inflammatory effects of fluoxetine in lipopolysaccharide(LPS)-stimulated microglial cells.
abstract: Recent evidence has suggested that microglial activation plays an important role in the pathogenesis of depression. Activated microglia can secrete various pro-inflammatory cytokines and neurotoxic mediators, which may contribute to the development and maintenance of depression. Thus, inhibition of microglial activation may have a therapeutic benefit in the treatment of depression. In the present study, using BV2 microglial cell line and primary microglial culture, we investigated if fluoxetine, the most widely used antidepressant, can inhibit microglia activation. Our results showed that fluoxetine significantly inhibited lipopolysaccharide (LPS)-induced production of tumor necrosis factor-alpha (TNF-α), interleukin- 6 (IL-6) and nitric oxide (NO). By RT-PCR, the mRNA level of these pro-inflammatory cytokines and iNOS was also attenuated by fluoxetine. We further investigated the intracellular signaling mechanism regulating the production of pro-inflammatory cytokines and NO from LPS-activated microglia. The results showed that fluoxetine inhibited IκB-a degradation, phosphorylation and nuclear translocation of the p65 subunit of NF-κB, and phosphorylation of p38 mitogen-activated protein kinase (MAPK) in the LPS-stimulated microglia. Taken together, our results suggest that the therapeutic effects of fluoxetine are partially mediated by modulating microglial activation.
authors.affiliation: Institute of Medical Psychology, Shandong University School of Medicine, Jinan, Shandong, PR China.
authors.forename: Dexiang
authors.initials: D
authors.lastname: Liu
authors.forename: Zhen
authors.initials: Z
authors.lastname: Wang
authors.forename: Shangming
authors.initials: S
authors.lastname: Liu
authors.forename: Fuwu
authors.initials: F
authors.lastname: Wang
authors.forename: Shidou
authors.initials: S
authors.lastname: Zhao
authors.forename: Aijun
authors.initials: A
authors.lastname: Hao
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D002460:Cell Line; D002478:Cells, Cultured; D005473:Fluoxetine / Q000494:pharmacology*; D066298:In Vitro Techniques; D018836:Inflammation Mediators / Q000037:antagonists & inhibitors / Q000502:physiology; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors / Q000633:toxicity*; D051379:Mice; D008807:Mice, Inbred BALB C; D017628:Microglia / Q000187:drug effects* / Q000378:metabolism*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D018836:Inflammation Mediators; D008070:Lipopolysaccharides; D005473:Fluoxetine