P2Y11 receptor antagonist NF340 ameliorates inflammation in human fibroblast ‐like synoviocytes: An implication in rheumatoid arthritis

In this study, we report that P2Y11 receptor activity is required for cytokine‐induced inflammation in primary fibroblast‐like synoviocytes (FLS). P2Y11R is fairly expressed in primar y FLS isolated from healthy subjects and is elevated to around three‐ to four‐fold in rheumatoid arthritis‐derived FLS. The expression of P2Y11R is inducible upon IL‐1β treatment. Blockage of P2Y11R by its antagonist suppresses IL‐1β‐induced TNF‐α and IL‐6 induction and ameliorate s oxidative stress as determined by levels of cellular ROS and the oxidative byproduct 4‐HNE. Moreover, blockage of P2Y11R by NF340 inhibits IL‐1β‐induced matrix metalloproteinase protein expression as indicated by the levels of MMP‐1, MMP‐3, and MMP‐13. Mechanistically, blockage of P2Y 11R mitigates IL‐1β‐activated NFκB signaling, which was revealed by reduced IκBα phosphorylation, nuclear p65 accumulation, and NFκB promoter activity. Our study provides evidence of a protective mechanism of P2Y11R antagonist NF340 against cytokine‐induced inflammation. Therefore, target ing P2Y11R could have potential therapeutic implication in the treatment of RA.
Source: IUBMB Life - Category: Research Authors: Tags: RESEARCH COMMUNICATION Source Type: research