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-inflammato...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.展开更多
文摘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.
