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Effect of ebosin on modulating interleukin-1β-induced nflammatory responses in rat fibroblast-like synoviocytes

Cellular & Molecular Immunology 2016年第5期13卷 584-592页

作者： Yang Zhang Lifei Wang Liping Bai Rong Jiang Lianhong Guo Jianbo Wu Guifang Cheng Ren-Zhang Yuan Li Key Laboratory of Biotechnology of Antibiotics Ministry of Health Institute of Medicinal Biotechnology Chinese Academy of Medical Sciences and Peking Union Medical College Beijing 100050 China Institute of Materia Medica Chinese Academy of Medical Sciences and Peking Union Medical College Beijing 100050 China School of Biological Sciences University of Wollongong Wollongong NSW 2522 Australia

The interleukin-1β-mitogen-activated protein kinase （MAPK） and NF-κB signaling pathways are involved in the pathogenesis of rheumatoid arthritis. Ebosin, a novel exopolysaccharide （EPS）, exhibits anti-inflammatory activity in rat collagen-induced arthritis by suppressing the production of tumor necrosis factor-s, interleukin-6 and interleukin-1β. The aim of the present study was to assess the effects of ebosin on NF-KB and MAPK signaling pathways mediated through interleukin-1β. in rat fibroblast-like synoviocytes （FLSs）. Western blotting showed decreased production of phosphorylated p38, JNK1, JNK2, IKKa, IKKa, and IκB in the cytoplasm and NF-κB in the nucleus upon ebosin treatment. The DNA-binding activity of NF-KB in the cell nucleus was also inhibited by ebosin treatment, as demonstrated using an electrophoresis mobility gel shift assay. Analysis of the results of the immunofluorescence assay also showed a reduced amount of NF-KB in the nucleus of cells affected by ebosin. These results provided evidence for the effects of ebosin on both interleukin-1β-mediated MAPK and NF-κB signaling pathways in rat FLSs. In addition, enzyme-linked immunosorbent assay demonstrated that ebosin reduces the levels of matrix metalloproteinases MMP-1 and MMP-3 and the chemokines, interleukin-8 and RANTES. Thus, the results of the present study provide further evidence for understanding the medicinal activity of ebosin at a molecular level, therefore nominating this EPS as a potential therapeutic candidate for the treatment of rheumatic arthritis.

关键词： interleukin-1β-mitogen-activated protein kinase

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