2. Academic Validation
  3. The protective effects of lixisenatide against inflammatory response in human rheumatoid arthritis fibroblast-like synoviocytes

The protective effects of lixisenatide against inflammatory response in human rheumatoid arthritis fibroblast-like synoviocytes

  • Int Immunopharmacol. 2019 Oct:75:105732. doi: 10.1016/j.intimp.2019.105732.
Xingye Du 1,  Hailin Zhang 2,  Wenhao Zhang 3,  Qing Wang 3,  Wei Wang 3,  Gaoren Ge 3,  Jiaxiang Bai 3,  Xiaobin Guo 3,  Yunqing Zhang 2,  Xuefeng Jiang 2,  Jiaye Gu 2,  Yaozeng Xu 4,  Dechun Geng 5
Affiliations

Affiliations

  • 1 Department of Orthopedics, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, China; Department of Orthopedics, Jiangyin Hospital Affiliated to Southeast University, Wuxi 214400, China.
  • 2 Department of Orthopedics, Jiangyin Hospital Affiliated to Southeast University, Wuxi 214400, China.
  • 3 Department of Orthopedics, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, China.
  • 4 Department of Orthopedics, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, China. Electronic address: [email protected].
  • 5 Department of Orthopedics, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, China. Electronic address: [email protected].
PMID: 31336333 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.

Keywords

Fibroblast-like synoviocytes (FLSs); Inflammatory response; Interleukin 1β (IL-1β); Lixisenatide; Matrix metalloproteinases (MMPs); NF-κB signaling pathway; Rheumatoid arthritis (RA).

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