Effect of usnic acid on HMGB1/RAGE inflammatory pathway in fibroblast-like synoviocytes of RA and VEGF,IL-6 and IL-1β expression levels
Objective To construct the rheumatoid arthritis fibroblast-like synoviocytes(RAFLS)model,and to investigate the effects of usnic acid on the inflammatory pathway of high-mobility group protein B1(HMGB1)/receptor for activated glycation end products(RAGE)and the expression levels of vascular en-dothelial growth factor(VEGF),interleukin(IL)-6 and IL-1β.Methods The patients with RA undergoing joint replacement surgery in the orthopedic department of the Second Affiliated Hospital of Guizhou Universi-ty of Traditional Chinese Medicine were selected and the synovial tissues were obtained during operation.The cells were divided into the blank control group(fetal calf serum),solvent control group(fetal calf serum+10%hydroxypropyl betacyclodextrin),usnic acid high dose group(usnic acid 50 μg/mL),usnic acid middle dose group(usnic acid 10 μg/mL),usnic acid low dose group(usnic acid 2.5 μg/mL)and hydroxychloroquine group(hydroxychloroquine 50 mmol/L).The cell proliferation after different concentrations of usnic acid treatment was detected by MTT,the HMGB1 and RAGE protein expression in cells of each group was detec-ted by Western blot,and the expression levels of HMGB1,VEGF,IL-6 and IL-1β were detected by ELISA.Re-sults Compared with the blank control group,the proportions of cellular apoptosis in the usnic acid high,middle and low doses groups and hydroxychloroquine group were increased(P<0.05);the expression levels of HMGB1 and RAGE protein in the usnic acid high,middle and low doses groups and hydroxychloroquine group were significantly decreased(P<0.05),the expression levels of HMGB1,VEGF,IL-6 and IL-1β were decreased(P<0.05);compared with the hydroxychloroquine group,the cellular apoptosis proportions of the usnic acid high,middle and low doses groups were decreased(P<0.05),the HMGB1 protein expression level in the usnic acid low dose group was significantly increased(P<005),the RAGE protein expression level in the the usnic acid middle amd low doses groups was significantly increased(P<0.05).Conclusion Usnic acid alleviates the inflammatory reaction of synoviocytes possibly by regulating HMGB1/RAGE inflammatory pathway and VEGF,IL-6 and IL-1β inflammatory factors expression levels.
rheumatoid arthritisusnic acidhigh mobility group box-1 proteinthe receptor of ad-vanced glycation end products