Aging
Navigate
Submit an Article
Research Paper|Volume 16, Issue 2|pp 1829—1844

IL-17 promotes IL-18 production via the MEK/ERK/miR-4492 axis in osteoarthritis synovial fibroblasts

Kun-Tsan Lee1,2, Chih-Yang Lin3, Shan-Chi Liu4, Xiu-Yuan He5, Chun-Hao Tsai6,7, Chih-Yuan Ko6,8, Yuan-Hsin Tsai9, Chia-Chia Chao10, Po-Chun Chen3,11, Chih-Hsin Tang5,12,13,14
  • 1Department of Post-Baccalaureate Medicine, National Chung-Hsing University, Taichung, Taiwan
  • 2Department of Orthopedics, Taichung Veterans General Hospital, Taichung, Taiwan
  • 3Translational Medicine Center, Shin-Kong Wu Ho-Su Memorial Hospital, Taipei City, Taiwan
  • 4Institute of Biomedical Sciences, Mackay Medical College, New Taipei City, Taiwan
  • 5Department of Pharmacology, School of Medicine, China Medical University, Taichung, Taiwan
  • 6Department of Orthopedic Surgery, China Medical University Hospital, Taichung, Taiwan
  • 7Department of Sports Medicine, College of Health Care, China Medical University, Taichung, Taiwan
  • 8Graduate Institute of Biomedical Science, China Medical University, Taichung, Taiwan
  • 9Department of Orthopedics, Show-Chwan Memorial Hospital, Changhua, Taiwan
  • 10Department of Respiratory Therapy, Fu-Jen Catholic University, New Taipei City, Taiwan
  • 11School of Life Science, National Taiwan Normal University, Taipei, Taiwan
  • 12Chinese Medicine Research Center, China Medical University, Taichung, Taiwan
  • 13Department of Medical Laboratory Science and Biotechnology, College of Health Science, Asia University, Taichung, Taiwan
  • 14Department of Medical Research, China Medical University Hsinchu Hospital, Hsinchu, Taiwan
Received: August 19, 2023Accepted: December 7, 2023Published: January 22, 2024
https://doi.org/10.18632/aging.205462

Copyright: © 2024 Lee et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

The concept of osteoarthritis (OA) as a low-grade inflammatory joint disorder has been widely accepted. Many inflammatory mediators are implicated in the pathogenesis of OA. Interleukin (IL)-18 is a pleiotropic cytokine with versatile cellular functions that are pathogenetically important in immune responses, as well as autoimmune, inflammatory, and infectious diseases. IL-17, a proinflammatory cytokine mainly secreted by Th17 cells, is upregulated in OA patients. However, the role of IL-17 in OA progression is unclear. The synovial tissues collected from healthy donors and OA patients were used to detect the expression level of IL-18 by IHC stain. The OA synovial fibroblasts (OASFs) were incubated with recombinant IL-17 and subjected to Western blot, qPCR, and ELISA to examine IL-18 expression level. The chemical inhibitors and siRNAs which targeted signal pathways were used to investigate signal pathways involved in IL-17-induced IL-18 expression. The microRNAs which participated IL-18 expression were surveyed with online databases miRWalk and miRDB, followed by validation with qPCR. This study revealed significantly higher levels of IL-18 expression in synovial tissue from OA patients compared with healthy controls, as well as increased IL-18 expression in OASFs from rats with severe OA. In vitro findings indicated that IL-17 dose-dependently promoted IL-18 production in OASFs. Molecular investigations revealed that the MEK/ERK/miR-4492 axis stimulated IL-18 production when OASFs were treated with IL-17. This study provides novel insights into the role of IL-17 in the pathogenesis of OA, which may help to inform OA treatment in the future.