The P2X7 receptor (P2X7R)-specific antagonist A804598 inhibits inflammatory reaction in human fibroblast-like synoviocytes.

The P2X7 receptor (P2X7R)-specific antagonist A804598 inhibits inflammatory reaction in human fibroblast-like synoviocytes. Am J Transl Res. 2020;12(1):45-53 Authors: Liu Y, Wu Y, Gu S, Yin Q, Li H, Wang J, Geng D, Xu Y Abstract Activation of the P2X7 receptor (P2X7R) has been found to increase expression of tumor necrosis factor-α (TNF-α) in the joints and synovial lining of patients with rheumatoid arthritis (RA). Increased expression of TNF-α promotes joint destruction through deterioration of type II collagen by matrix metalloproteinases (MMPs), expression of proinflammatory cytokines, oxidative stress, and activation of cellular signaling pathways. In the present study, we exposed fibroblast-like synoviocytes (FLSs) to TNF-α in the presence and absence of the P2X7R antagonist A804598. We then employed real time PCR and western blot analysis to analyze the mRNA and protein expression levels of P2X7R in both control and RA-FLSs. We confirmed that P2X7R is expressed on FLSs and is upregulated in RA-FLSs and FLSs exposed to TNF-α. Importantly, we also demonstrate the ability of P2X7R antagonism using A804598 to suppress oxidative stress, expression of interleukin (IL)-1β, IL-6, MMP-1, MMP-3, MMP-13 as well as activation of the Janus family of tyrosine kinase/signal transducer and activator of transcription (JAK1/STAT3) proinflammatory signaling pathway. These findings implicate a novel role of antagonism of P2X7R as a t...
Source: American Journal of Translational Research - Category: Research Tags: Am J Transl Res Source Type: research

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