Rebamipide Suppresses Monosodium Urate Crystal-Induced Interleukin-1β Production Through Regulation of Oxidative Stress and Caspase-1 in THP-1 Cells

This study investigated the effect of rebamipide on activation of the NLRP3 inflammasome and generation of reactive oxygen species (ROS) in monosodium urate (MSU) crystal-induced interleukin-1 beta (IL-1 beta) production. Human monocyte cell line THP-1 and human umbilical venous endothelial cells (HUVECs) were used to assess the inflammatory response to MSU crystals. NADP/NADPH activity assays were used as a marker of ROS generation. Quantitative real-time polymerase chain reaction (qRT-PCR) and western blotting were performed to evaluate levels of IL-1 beta, caspase-1, NLRP3, associated speck-like protein (ASC), nuclear factor-kappa B (NF-kappa B), p65, I kappa B alpha, intercellular adhesion molecule 1 (ICAM-1), and vascular cell adhesion molecule 1 (VCAM-1). Experimental pharmaceuticals included rebamipide, colchicine, dexamethasone, and ascorbic acid. In THP-1 cells, treatment with MSU crystals increased NADP/NADPH ratios and IL-1 beta expression, and both of these responses were potently inhibited by addition of rebamipide. Rebamipide also attenuated enhanced expression of caspase-1 gene by MSU crystals (p < 0.05). Western blotting demonstrated that MSU crystals stimulated caspase-1 but not NLRP3 and ASC activation. Similarly, MSU crystals activated the NF-kappa B pathway, which in turn was blocked by rebamipide. Stimulation of HUVECs with MSU crystals increased expression of VCAM-1 and ICAM-1, which were markedly inhibited by both rebamipide and dexamethasone. This study demonstrated that rebamipide inhibits IL-1 beta activation through suppression of ROS-mediated NF-kappa B signaling pathways and caspase-1 activation in MSU crystal-induced inflammation.