1. Academic Validation
  2. Omp31 of Brucella Inhibits NF-κB p65 Signaling Pathway by Inducing Autophagy in BV-2 Microglia

Omp31 of Brucella Inhibits NF-κB p65 Signaling Pathway by Inducing Autophagy in BV-2 Microglia

  • Neurochem Res. 2021 Dec;46(12):3264-3272. doi: 10.1007/s11064-021-03429-4.
Zhao Wang  # 1 Guowei Wang  # 2 Yanbai Wang 2 Qiang Liu 2 Haining Li 2 Peng Xie 3 Zhenhai Wang 4 5
Affiliations

Affiliations

  • 1 Ningxia Medical University, Yinchuan, Ningxia Hui Autonomous Region, China.
  • 2 Neurology Center, The General Hospital of Ningxia Medical University, Yinchuan, Ningxia Hui Autonomous Region, China.
  • 3 The First Affiliated Hospital of Chongqing Medical University, Chongqing, China. xiepeng@cqmu.edu.cn.
  • 4 Neurology Center, The General Hospital of Ningxia Medical University, Yinchuan, Ningxia Hui Autonomous Region, China. wangzhenhai1968@163.com.
  • 5 Diagnosis and Treatment Engineering Technology Research Center of Nervous System Diseases of Ningxia Hui Autonomous Region, Yinchuan, Ningxia Hui Autonomous Region, China. wangzhenhai1968@163.com.
  • # Contributed equally.
Abstract

Neurobrucellosis is a serious central nervous system (CNS) inflammatory disorder caused by Brucella, and outer membrane protein-31 (Omp31) plays an important role in Brucella Infection. This study aims to determine whether Omp31 can induce Autophagy in BV-2 microglia. Another goal of the study is to further examine the effect of Autophagy on the nuclear transcription factor κB (NF-κB) p65 signaling pathway. We observed that Omp31 stimulated Autophagy by increasing microtubule-associated protein 1 LIGHT chain 3B (LC3B-II) levels and inducing autophagosome formation at 6 h and 12 h. Concomitantly, Omp31 induced tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) expression in a time-dependent manner but reduced the expression of TNF-α at 6 h. We utilized Omp31 with or without rapamycin or 3-methyladenine (3-MA) to treat BV-2 microglia, and it demonstrated further that Omp31 induced Autophagy by promoting LC3B-II, Beclin-1 proteins expression and inhibiting the p62 protein levels. Furthermore, we explored the effects of Autophagy on the NF-κB p65 pathway through western blot analysis, RT-qPCR assay, enzyme-linked immunosorbent assay (ELISA) and immunofluorescence. The data suggest that Omp31 as well as rapamycin, the Autophagy inducer, can decrease TNF-α levels through the inhibition of the NF-κB p65 signaling pathway. Taken together, Omp31 can function as a catalyst in both Autophagy induction and NF-κB p65 signal inhibition. Furthermore, Omp31-induced Autophagy may inhibit the expression of TNF-α by negatively regulating NF-κB p65 signaling pathway.

Keywords

Autophagy; BV-2 microglia; Brucella melitensis; NF-κB p65; Omp31.

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