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 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.

• Authors: Hong Ki Min, Ji-Yeon Won, Bo-Mi Kim, Kyung-Ann Lee, Seoung-Joon Lee, Sang-Heon Lee, Hae-Rim Kim, Kyoung-Woon Kim
• Journal: Arthritis research & therapy (Arthritis Res Ther) Vol. 22 Issue 1 Pg. 222 (09 23 2020) ISSN: 1478-6362 [Electronic] England
• PMID: 32972460 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Interleukin-17
• Interleukins
• RANK Ligand
• STAT3 Transcription Factor
• STAT3 protein, human
• NF-KappaB Inhibitor alpha
• p38 Mitogen-Activated Protein Kinases

Topics

• Arthritis, Rheumatoid
• Cells, Cultured
• Fibroblasts (metabolism)
• Humans
• Interleukin-17
• Interleukins (metabolism)
• NF-KappaB Inhibitor alpha
• Osteoclasts (metabolism)
• Osteogenesis
• RANK Ligand (metabolism)
• STAT3 Transcription Factor
• Synovial Membrane (metabolism)
• p38 Mitogen-Activated Protein Kinases
• Interleukin-22