%0 Journal Article
%T The protective effects of lixisenatide against inflammatory response in human rheumatoid arthritis fibroblast-like synoviocytes.
%A Du X
%A Zhang H
%A Zhang W
%A Wang Q
%A Wang W
%A Ge G
%A Bai J
%A Guo X
%A Zhang Y
%A Jiang X
%A Gu J
%A Xu Y
%A Geng D
%J Int Immunopharmacol
%V 75
%N 0
%D Oct 2019
%M 31336333
%F 5.714
%R 10.1016/j.intimp.2019.105732
%X Rheumatoid arthritis (RA) is a major debilitating systemic disease characterized by chronic inflammation of the synovium and joint destruction. Despite major advancements in our understanding of RA in recent decades, it remains a disease of unknown etiology. To our knowledge, this is the first study exploring the effects of agonism of the glucagon-like peptide-1 (GLP-1) receptor using lixisenatide, a licensed drug used for the treatment of type II diabetes, on the pathological characteristics of RA in human fibroblast-like synoviocytes. Our findings indicate that lixisenatide inhibited the inflammatory response through downregulation of proinflammatory cytokines, such as tumor necrosis factor α (TNF-α), interleukin-6 (IL-6), and interleukin-8 (IL-8); inhibition of matrix metalloproteinases (MMPs); and blockade of cellular signaling pathways, including the c-Jun N-terminal kinase (JNK), activator protein 1 (AP-1), and nuclear factor κ B (NF-κB) pathways. Furthermore, lixisenatide improved oxidative stress, rescued mitochondrial membrane potential (ΔΨm), and prevented cell death in fibroblast-like synoviocytes. These findings suggest that agonism of the GLP-1 receptor using lixisenatide may serve as a novel therapeutic option for the treatment and prevention of RA.