Hesperidin inhibits synovial cell inflammation and macrophage polarization through suppression of the PI3K/AKT pathway in complete Freund's adjuvant-induced arthritis in mice
Autor: | Daozhang Cai, Chang Zhao, Fan Kai, Weizhong Qi, Haiyan Zhang, Liangliang Liu, Xiaofeng Feng, Hang Fang, Yan Shao, Rongkai Zhang, Ziyu Chen, Chuangxin Lin |
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Rok vydání: | 2019 |
Předmět: |
Lipopolysaccharides
Male musculoskeletal diseases 0301 basic medicine MMP3 Freund's Adjuvant Macrophage polarization Arthritis Inflammation MMP9 Toxicology Proinflammatory cytokine Arthritis Rheumatoid Mice Phosphatidylinositol 3-Kinases 03 medical and health sciences 0302 clinical medicine Synovitis medicine Animals PI3K/AKT/mTOR pathway Phosphoinositide-3 Kinase Inhibitors Chemistry Hesperidin Macrophages General Medicine medicine.disease Synoviocytes Mice Inbred C57BL 030104 developmental biology 030220 oncology & carcinogenesis Cancer research medicine.symptom Proto-Oncogene Proteins c-akt |
Zdroj: | Chemico-Biological Interactions. 306:19-28 |
ISSN: | 0009-2797 |
Popis: | Rheumatoid arthritis (RA) is an autoimmune disease characterized by synovitis. Synovitis can cause joint injury by releasing inflammatory factors and metalloproteinases (MMPs). Therefore, it is necessary to find drugs that can control synovitis in the process of RA. Herein, we investigate the anti-inflammatory effect of Hesperidin (HSN) on fibroblast-like synovial (FLS) cells induced by lipopolysaccharide (LPS) and the protective action of M1 polarization level of synovial macrophages on antigen-induced arthritis (AIA) in order to elucidate the reduction of inflammatory cytokines and MMPs and the inhibition of macrophage activation. The functional effect of HSN on LPS-induced mRNA and protein expressions of inflammatory cytokines and MMPs in FLS cells as well as on LPS-induced macrophage M1 and M2 polarization markers was determined by quantitative real-time PCR (qPCR) or Western blot analyses, respectively. AIA in 2-month-old mice was generated using intraperitoneal injection with HSN (20 mg/kg/day) or LY294002 (20 mg/kg/day). The results show HSN significantly inhibited the LPS-induced gene expression of the inflammatory mediators. Furthermore, treatment with HSN relieved the antigen-induced arthritis and reduced the protein levels of MMP3, MMP9, and MMP13 in FLS and inhibited the polarization of macrophages to M1. Based on the results of our analyses, we concluded that HSN has significant anti-inflammatory activities and reduces the potential of MMPs in rheumatoid arthritis and the degree of polarization of macrophages to M1. Through the study of signaling pathways, we established that the inhibition of the PI3K/AKT signaling pathway by HSN may show therapeutic effects in the progression of rheumatoid arthritis. |
Databáze: | OpenAIRE |
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