title: Rifampicin inhibits microglial inflammation and improves neuron survival against inflammation.
abstract: Microglial activation plays an important role in the pathophysiology of neurodegenerative diseases, and suppression of microglial activation prevents the progression of neurodegeneration. Rifampicin, a bacteriocidal antibiotic, induces immunosuppression. We hypothesized that rifampicin might be neuroprotective by inhibiting the production of pro-inflammatory mediators, thereby suppressing microglial activation. In the present study, we examined the effects of rifampicin on the production of lipopolysaccharide (LPS)-induced pro-inflammatory mediators and their signaling pathways in BV2 microglia. We also assessed the neuroprotective effects of rifampicin using a co-culture of microglia and neurons. Our results showed that rifampicin inhibited the LPS-stimulated expression of inducible nitric oxide synthase, cyclooxygenase-2, tumor necrosis factor-α, and interleukin-1β, as well as the production of nitric oxide and prostaglandin E₂. Moreover, rifampicin suppressed LPS-induced nuclear factor-kappa B activation by blocking the degradation of the inhibitor of the nuclear transcription factor NF-kappa B. Rifampicin inhibited the phosphorylation of mitogen activated protein kinases, although protein kinase B was not inhibited. Preincubation of microglia with rifampicin reduced neurotoxicity and improved neuron survival in a microglia-neuronal co-culture system. Taken together, these findings suggest that rifampicin, with its anti-inflammatory properties, might be a novel treatment for neurodegenerative diseases.
authors.affiliation: Department of Neurology, Sun Yat-sen memorial Hospital, Sun Yat-sen University, Guangzhou 510120, PR China.
authors.forename: Wei
authors.initials: W
authors.lastname: Bi
authors.forename: Lihong
authors.initials: L
authors.lastname: Zhu
authors.forename: Chuanming
authors.initials: C
authors.lastname: Wang
authors.forename: Yanran
authors.initials: Y
authors.lastname: Liang
authors.forename: Jun
authors.initials: J
authors.lastname: Liu
authors.forename: Qiaoyun
authors.initials: Q
authors.lastname: Shi
authors.forename: Enxiang
authors.initials: E
authors.lastname: Tao
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology* / Q000627:therapeutic use; D002461:Cell Line, Transformed; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D018920:Coculture Techniques; D007249:Inflammation / Q000473:pathology / Q000517:prevention & control; D018836:Inflammation Mediators / Q000494:pharmacology*; D051379:Mice; D017628:Microglia / Q000187:drug effects* / Q000473:pathology*; D019636:Neurodegenerative Diseases / Q000188:drug therapy* / Q000473:pathology; D009474:Neurons / Q000187:drug effects / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012293:Rifampin / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D018836:Inflammation Mediators; D012293:Rifampin