2. Academic Validation
  3. CXCL1 contributes to IL-6 expression in osteoarthritis and rheumatoid arthritis synovial fibroblasts by CXCR2, c-Raf, MAPK, and AP-1 pathway

CXCL1 contributes to IL-6 expression in osteoarthritis and rheumatoid arthritis synovial fibroblasts by CXCR2, c-Raf, MAPK, and AP-1 pathway

  • Arthritis Res Ther. 2020 Oct 21;22(1):251. doi: 10.1186/s13075-020-02331-8.
Sheng-Mou Hou 1,  Po-Chun Chen 2 3 4,  Chieh-Mo Lin 5 6 7,  Mei-Ling Fang 8 9,  Miao-Ching Chi 10 11 12,  Ju-Fang Liu 13
Affiliations

Affiliations

  • 1 Department of Orthopedic Surgery, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, 111, Taiwan.
  • 2 Translational Medicine Center, Shin-Kong Wu Ho-Su Memorial Hospital, Taipei, 111, Taiwan.
  • 3 Department of Biotechnology, College of Medical and Health Science, Asia University, Taichung, 413, Taiwan.
  • 4 Department of Medical Research, China Medical University Hospital, China Medical University, Taichung, 404, Taiwan.
  • 5 Department of Nursing, Chang Gung University of Science and Technology, Puzi City, 613, Chiayi County, Taiwan.
  • 6 Division of Pulmonary and Critical Care Medicine, Chang Gung Memorial Hospital, Puzi City, 613, Chiayi County, Taiwan.
  • 7 Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Taoyuan, 333, Taiwan.
  • 8 Center for Environmental Toxin and Emerging-Contaminant Research, Cheng Shiu University, Kaohsiung, 833, Taiwan.
  • 9 Super Micro Research and Technology Center, Cheng Shiu University, Kaohsiung, 833, Taiwan.
  • 10 Chronic Disease and Health Promotion Research Center, Chang Gung University of Science and Technology, Puzi City, 613, Chiayi County, Taiwan. [email protected].
  • 11 Division of Pulmonary and Critical Care Medicine, Chiayi Chang Gung Memorial Hospital, Puzi City, 613, Chiayi County, Taiwan. [email protected].
  • 12 Department of Respiratory Care, Chang Gung University of Science and Technology, Puzi City, 613, Chiayi County, Taiwan. [email protected].
  • 13 School of Oral Hygiene, College of Oral Medicine, Taipei Medical University, No. 250 Wu-Hsing Street, Taipei, 110, Taiwan. [email protected].
PMID: 33087182 DOI: 10.1186/s13075-020-02331-8
Abstract

Background: Osteoarthritis (OA) and rheumatoid arthritis (RA) are common joint disorders that are considered to be different diseases due to their unique molecular mechanisms and pathogenesis. Chemokines and their corresponding receptors have been well characterized in RA progression, but less so in OA pathogenesis.

Methods: The human primary synovial fibroblasts (SFs) were obtained from human OA and RA tissue samples. The Western blot and qPCR were performed to analyze the expression levels of CXCL1, as well as CXCL-promoted IL-6 expression in both OASFs and RASFs. The signal cascades that mediate the CXCL1-promoted IL-6 expression were identified by using chemical inhibitors, siRNAs, and shRNAs.

Results: Here, we found that both diseases feature elevated levels of CXCL1 and interleukin (IL)-6, an important proinflammatory cytokine that participates in OA and RA pathogenesis. In OASFs and RASFs, CXCL1 promoted IL-6 expression in a dose- and time-dependent manner. In OASFs and RASFs overexpressing CXCL1 or transduced with shRNA plasmid, IL-6 expression was markedly upregulated. CXCR2, c-Raf, and MAPKs were found to regulate CXCL1-induced IL-6 expression in OASFs and RASFs. Finally, CXCL1 triggered the transcriptional activities of c-Jun (which regulates the expression of proinflammatory proteins) in OASFs and RASFs.

Conclusions: Our present work suggests that the CXCL1/CXCR2 axis helps to orchestrate inflammatory responses in OA and RA SFs.

Keywords

CXCL1; IL-6; Osteoarthritis; Rheumatoid arthritis.

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