PM2.5 facilitates IL-6 production in human osteoarthritis synovial fibroblasts via ASK1 activation

Ju Fang Liu, Miao Ching Chi, Chih Yang Lin, Chiang Wen Lee, Tsung Ming Chang, Chien Kuo Han, Yuan Li Huang, Yi Chin Fong, Hsien Te Chen, Chih Hsin Tang

Research output: Contribution to journalArticle

Abstract

Osteoarthritis (OA) is a progressive degenerative joint disorder characterized by synovial inflammation. Interleukin-6 (IL-6) is a key proinflammatory cytokine in OA progression. Particulate matter 2.5 (PM2.5) exposure increases the risk of different diseases, including OA. Up until now, no studies have described any association between PM2.5 and IL-6 expression in human OA synovial fibroblasts (OASFs). Here, our data show that PM2.5 concentration- and time-dependently promoted IL-6 synthesis in human OASFs. We also found that reactive oxygen species (ROS) generation potentiated the effects of PM2.5 on IL-6 production. ASK1, ERK, p38, and JNK inhibitors reduced PM2.5-induced increases of IL-6 expression. Treatment of OASFs with PM2.5 promoted phosphorylation of these signaling cascades. We also found that PM2.5 enhanced c-Jun phosphorylation and its translocation into the nucleus. Thus, PM2.5 increases IL-6 production in human OASFs via the ROS, ASK1, ERK, p38, JNK, and AP-1 signaling pathways. Our evidence links PM2.5 with OA progression.

Original languageEnglish
JournalJournal of Cellular Physiology
DOIs
Publication statusAccepted/In press - 2020

Keywords

  • ASK1
  • IL-6
  • osteoarthritis
  • PM2.5
  • ROS

ASJC Scopus subject areas

  • Physiology
  • Clinical Biochemistry
  • Cell Biology

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  • Cite this

    Liu, J. F., Chi, M. C., Lin, C. Y., Lee, C. W., Chang, T. M., Han, C. K., Huang, Y. L., Fong, Y. C., Chen, H. T., & Tang, C. H. (Accepted/In press). PM2.5 facilitates IL-6 production in human osteoarthritis synovial fibroblasts via ASK1 activation. Journal of Cellular Physiology. https://doi.org/10.1002/jcp.30009