Inhibition of 26S Protease Regulatory Subunit 7 MSS1 Suppresses NeuroinflammationReport as inadecuate




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Recently, researchers have focused on immunosuppression induced by rifampicin. Our previous investigation found that rifampicin was neuroprotective by inhibiting the production of pro-inflammatory mediators, thereby suppressing microglial activation. In this study, using 2-dimensional gel electrophoresis 2-DE and mass spectrometry MS, we discovered that 26S protease regulatory subunit 7 MSS1 was decreased in rifampicin-treated microglia. Western blot analysis verified the downregulation of MSS1 expression by rifampicin. As it is indicated that the modulation of the ubiquitin-26S proteasome system UPS with proteasome inhibitors is efficacious for the treatment of neuro-inflammatory disorders, we next hypothesized that silencing MSS1 gene expression might inhibit microglial inflammation. Using RNA interference RNAi, we showed significant reduction of IkBα degradation and NF-kB activation. The production of lipopolysaccharides-induced pro-inflammatory mediators such as inducible nitric oxide synthase iNOS, nitric oxide, cyclooxygenase-2, and prostaglandin E2 were also reduced by MSS1 gene knockdown. Taken together, our findings suggested that rifampicin inhibited microglial inflammation by suppressing MSS1 protein production. Silencing MSS1 gene expression decreased neuroinflammation. We concluded that MSS1 inhibition, in addition to anti-inflammatory rifampicin, might represent a novel mechanism for the treatment of neuroinflammatory disorders.



Author: Wei Bi , Xiuna Jing , Lihong Zhu, Yanran Liang, Jun Liu, Lianhong Yang, Songhua Xiao, Anding Xu, Qiaoyun Shi, Enxiang Tao

Source: http://plos.srce.hr/



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