کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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4325906 | 1614044 | 2011 | 9 صفحه PDF | دانلود رایگان |
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.
Research highlights
► Rifampicin is an effective antiinflammatory agent.
► Rifampicin can inhibit the production of proinflammory factors through downregulation of NF-κB and MAPKs pathway.
► Rifampicin may have a possible therapeutic application in the treatment of neuroinflammatory disorders.
Journal: Brain Research - Volume 1395, 13 June 2011, Pages 12–20