Interleukin (IL)-25 suppresses IL-22-induced osteoclastogenesis in rheumatoid arthritis via STAT3 and p38 MAPK/IκBα pathway
Abstract 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...
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| Format: | Article |
| Language: | English |
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BMC
2020-09-01
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| Series: | Arthritis Research & Therapy |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s13075-020-02315-8 |
| _version_ | 1819116334782349312 |
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| author | Hong Ki Min Ji-Yeon Won Bo-Mi Kim Kyung-Ann Lee Seoung-Joon Lee Sang-Heon Lee Hae-Rim Kim Kyoung-Woon Kim |
| author_facet | Hong Ki Min Ji-Yeon Won Bo-Mi Kim Kyung-Ann Lee Seoung-Joon Lee Sang-Heon Lee Hae-Rim Kim Kyoung-Woon Kim |
| author_sort | Hong Ki Min |
| collection | DOAJ |
| description | Abstract 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. |
| first_indexed | 2024-12-22T05:15:27Z |
| format | Article |
| id | doaj.art-54ec51cf80d44355b40cdf83c3ebe0a9 |
| institution | Directory Open Access Journal |
| issn | 1478-6362 |
| language | English |
| last_indexed | 2024-12-22T05:15:27Z |
| publishDate | 2020-09-01 |
| publisher | BMC |
| record_format | Article |
| series | Arthritis Research & Therapy |
| spelling | doaj.art-54ec51cf80d44355b40cdf83c3ebe0a92022-12-21T18:37:52ZengBMCArthritis Research & Therapy1478-63622020-09-0122111110.1186/s13075-020-02315-8Interleukin (IL)-25 suppresses IL-22-induced osteoclastogenesis in rheumatoid arthritis via STAT3 and p38 MAPK/IκBα pathwayHong Ki Min0Ji-Yeon Won1Bo-Mi Kim2Kyung-Ann Lee3Seoung-Joon Lee4Sang-Heon Lee5Hae-Rim Kim6Kyoung-Woon Kim7Division of Rheumatology, Department of Internal Medicine, Konkuk University Medical CenterR&D Center, OncoInsightLaboratory of Stem Cell, NEXELDivision of Rheumatology, Department of Internal Medicine, Soonchunhyang University HospitalDepartment of Orthopedic Surgery, School of Medicine, Konkuk UniversityDivision of Rheumatology, Department of Internal Medicine, Research Institute of Medical Science, School of Medicine, Konkuk UniversityDivision of Rheumatology, Department of Internal Medicine, Research Institute of Medical Science, School of Medicine, Konkuk UniversityR&D Center, OncoInsightAbstract 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.http://link.springer.com/article/10.1186/s13075-020-02315-8Rheumatoid arthritisOsteoclastogenesisIL-22IL-25 |
| spellingShingle | Hong Ki Min Ji-Yeon Won Bo-Mi Kim Kyung-Ann Lee Seoung-Joon Lee Sang-Heon Lee Hae-Rim Kim Kyoung-Woon Kim Interleukin (IL)-25 suppresses IL-22-induced osteoclastogenesis in rheumatoid arthritis via STAT3 and p38 MAPK/IκBα pathway Arthritis Research & Therapy Rheumatoid arthritis Osteoclastogenesis IL-22 IL-25 |
| title | Interleukin (IL)-25 suppresses IL-22-induced osteoclastogenesis in rheumatoid arthritis via STAT3 and p38 MAPK/IκBα pathway |
| title_full | Interleukin (IL)-25 suppresses IL-22-induced osteoclastogenesis in rheumatoid arthritis via STAT3 and p38 MAPK/IκBα pathway |
| title_fullStr | Interleukin (IL)-25 suppresses IL-22-induced osteoclastogenesis in rheumatoid arthritis via STAT3 and p38 MAPK/IκBα pathway |
| title_full_unstemmed | Interleukin (IL)-25 suppresses IL-22-induced osteoclastogenesis in rheumatoid arthritis via STAT3 and p38 MAPK/IκBα pathway |
| title_short | Interleukin (IL)-25 suppresses IL-22-induced osteoclastogenesis in rheumatoid arthritis via STAT3 and p38 MAPK/IκBα pathway |
| title_sort | interleukin il 25 suppresses il 22 induced osteoclastogenesis in rheumatoid arthritis via stat3 and p38 mapk iκbα pathway |
| topic | Rheumatoid arthritis Osteoclastogenesis IL-22 IL-25 |
| url | http://link.springer.com/article/10.1186/s13075-020-02315-8 |
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