Interleukin (IL)-25 suppresses IL-22-induced osteoclastogenesis in rheumatoid arthritis via STAT3 and p38 MAPK/IκBα pathway
| Autor: | Hong Ki Min, Kyung-Ann Lee, Kyoung-Woon Kim, Hae-Rim Kim, Bo-Mi Kim, Ji-Yeon Won, Seoung-Joon Lee, Sang-Heon Lee |
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| Rok vydání: | 2020 |
| Předmět: |
STAT3 Transcription Factor
0301 basic medicine lcsh:Diseases of the musculoskeletal system Osteoclastogenesis Osteoclasts p38 Mitogen-Activated Protein Kinases Arthritis Rheumatoid Interleukin 22 03 medical and health sciences IL-25 0302 clinical medicine NF-KappaB Inhibitor alpha Osteogenesis Osteoclast IL-22 medicine Humans Synovial fluid Rheumatoid arthritis STAT3 Receptor Cells Cultured 030203 arthritis & rheumatology biology Chemistry Interleukins Interleukin-17 RANK Ligand Synovial Membrane Interleukin Fibroblasts IκBα 030104 developmental biology medicine.anatomical_structure RANKL biology.protein Cancer research lcsh:RC925-935 Research Article |
| Zdroj: | Arthritis Research & Therapy, Vol 22, Iss 1, Pp 1-11 (2020) Arthritis Research & Therapy |
| ISSN: | 1478-6362 |
| DOI: | 10.1186/s13075-020-02315-8 |
| Popis: | Background The present study aimed to evaluate the suppressive role of interleukin (IL)-25 in IL-22-induced osteoclastogenesis and receptor activator of nuclear factor κB ligand (RANKL) expression in rheumatoid arthritis (RA). Methods Serum from patients with RA and osteoarthritis (OA), and healthy controls, and synovial fluid from patients with RA and OA were collected, and the levels of IL-22 and IL-25 were measured. RA and OA synovial tissues were stained against IL-25. Fibroblast-like synoviocytes (FLSs) of patients with RA were cultured with IL-22, in the presence or absence of IL-25, and RANKL expression was measured by real-time PCR and enzyme-linked immunosorbent assay (ELISA). Human peripheral blood monocytes were cultured under IL-22/RANKL + M-CSF, with or without IL-25, and tartrate-resistant acid phosphatase (TRAP)-positive cells and osteoclast-related markers were investigated to determine osteoclastogenesis. Results Serum and synovial IL-25 levels in RA were upregulated compared to those in OA and healthy control, and elevated expression of IL-25 in RA synovial tissue was re-confirmed. IL-25 and IL-22 levels showed significant correlation in serum and synovial fluid. Pre-treatment of FLS with IL-25 reduced IL-22-induced RANKL expression at the RNA level. The suppressive effects of IL-25 were confirmed to occur through the STAT3 and p38 MAPK/IκBα pathways. IL-25 reduced osteoclast differentiation and suppressed the expression of osteoclast-related markers. Conclusion In the current study, we demonstrated the regulatory effect of IL-25 on IL-22-induced osteoclastogenesis. Therapeutic approach involving augmentation of IL-25 regulatory response may serve as a novel treatment option for RA, especially by suppressing osteoclastogenesis. |
| Databáze: | OpenAIRE |
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