{Reference Type}: Journal Article
{Title}: The protective effects of lixisenatide against inflammatory response in human rheumatoid arthritis fibroblast-like synoviocytes.
{Author}: Du X;Zhang H;Zhang W;Wang Q;Wang W;Ge G;Bai J;Guo X;Zhang Y;Jiang X;Gu J;Xu Y;Geng D;
{Journal}: Int Immunopharmacol
{Volume}: 75
{Issue}: 0
{Year}: Oct 2019
{Factor}: 5.714
{DOI}: 10.1016/j.intimp.2019.105732
{Abstract}: 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.