Rifampicin inhibits microglial inflammation and improves neuron survival against inflammation

作者：Bi Wei; Zhu Lihong; Wang Chuanming; Liang Yanran; Liu Jun; Shi Qiaoyun; Tao Enxiang^*

来源：Brain Research, 2011, 1395: 12-20.

DOI：10.1016/j.brainres.2011.04.019

• Rifampicin
• Microglia
• NF-kappa B
• MAPKs
• Neuronal cell
• Neuroprotection

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-alpha, and interleukin-1 beta, as well as the production of nitric oxide and prostaglandin E(2). 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.

• 单位
  济南大学; 暨南大学