Session Type: ACR Poster Session C
Session Time: 9:00AM-11:00AM
Background/Purpose: This study investigated the effect of rebamipide on activation of NLRP3 inflammasome and reactive oxygen species (ROS) in monosodium urate (MSU) crystal-induced interleukin-1b (IL-1b) production.
Methods: Human monocyte cell line THP-1 cells and human umbilical venous endothelial cells (HUVECs) were used for assessing inflammatory response to MSU crystals. NADP/NADPH activity assay was used for an alternative marker for ROS generation. Quantitative Real-time polymerase chain reaction (qRT-PCR) and western blotting was performed to evaluate levels of IL-1b, caspase-1, NLRP3, ASC, nuclear factor-kB (NF-kB), IkB, intercellular adhesion molecule 1 (ICAM-1), or vascular cell adhesion molecule 1 (VCAM-1). Experimental pharmaceuticals included rebamipide, colchicine, dexamethasone, and ascorbic acid.
Results: MSU crystals treatment to THP-1 cells induced NADP/NADPH ratio and IL-1b expression, which was potently inhibited by addition of rebamipide. Rebamipide also significantly attenuated enhanced mRNA expression of caspase-1 by MSU crystals (p = 0.0033), in addition to colchicine and ascorbic acid (p = 0.0323 and p = 0.0266, respectively). Western blotting demonstrated that MSU crystals stimulated only caspase-1, but not NLRP3 and ASC activation. Similarly, MSU crystals activated NF-kB pathway, which in turn was blocked by rebamipide. Increased expression of VCAM-1 and ICAM-1 by stimulation of MSU crystals to HUVECs was markedly inhibited by rebamipide, in addition to dexamethasone.
Conclusion: This study demonstrated that rebamipide inhibits IL-1b activation through suppression of ROS-mediated NF-kB and caspase-1 activation in MSU crystal-induced inflammation.
To cite this abstract in AMA style:Choe JY, Her M, Kim SK. Rebamipide Suppresses Monosodium Urate Crystal-Induced Interleukin-1b Production through Regulation of Oxidative Stress and Caspase-1 in THP-1 Cells [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). https://acrabstracts.org/abstract/rebamipide-suppresses-monosodium-urate-crystal-induced-interleukin-1b-production-through-regulation-of-oxidative-stress-and-caspase-1-in-thp-1-cells/. Accessed July 11, 2020.
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/rebamipide-suppresses-monosodium-urate-crystal-induced-interleukin-1b-production-through-regulation-of-oxidative-stress-and-caspase-1-in-thp-1-cells/