Glibenclamide-sulfonylurea receptor 1 antagonist alleviates LPS-induced BV2 cell activation through the p38/MAPK pathway

作者：Xu, Zhiming; Liu, Yingliang; Yang, Dianxu; Yuan, Fang; Ding, Jun; Wang, Liping; Qu, Meijie; Yang, Guoyuan; Tian, Hengli^*

来源：RSC Advances, 2017, 7(44): 27206-27213.

DOI：10.1039/c7ra03042h

• TRAUMATIC BRAIN-INJURY
• NF-KAPPA-B
• SPINAL NERVE LIGATION
• NITRIC-OXIDE SYNTHASE
• SUBARACHNOID HEMORRHAGE
• MICROGLIAL ACTIVATION
• MECHANICAL ALLODYNIA
• BARRIER DISRUPTION
• K+-CHANNELS
• P38 MAPK

We investigated the anti-neuroinflammatory activity and mechanism of glibenclamide, sulfonylurea receptor 1 (Sur1) antagonist, against LPS-induced microglial activation in vitro. BV2 microglia cells were exposed to LPS (100 ng mL(-1)). iNOS and COX-2 levels, proinflammatory cytokine mRNA expression, and the p38/MAPK signaling pathway were analyzed by RT-PCR and Western blotting. Pretreatment with glibenclamide (2.5, 10, and 40 mu M) inhibited the LPS-induced overexpression of iNOS and COX-2 in BV2 microglia cells. Blocking Sur1 reduced intracellular reactive oxygen species (ROS) levels. Glibenclamide dose-dependently (2.5, 10 mM) decreased LPS-induced over-expression of TNF-alpha, IL-6, and IL-1 beta, and alleviated the intracellular calcium accumulation in LPS-treated BV2 microglia cells. Moreover, glibenclamide diminished the LPS-induced phosphorylation of p38/MAPK, SB203580, a selective p38/MAPK inhibitor, significantly potentiated glibenclamide-caused inhibition of the expression of iNOS and COX-2 in LPS-exposed BV2 cells. Glibenclamide-Sur1 antagonist exerts anti-inflammatory activity in murine microglia in vitro by inhibiting the p38/MAPK signaling pathways and proinflammatory responses. Glibenclamide may be developed as a novel agent for suppressing inflammatory responses in the central nervous system.

• 出版日期2017
• 单位上海交通大学; 上海市闵行区中心医院