IL-15 promotes osteoclastogenesis via the PLD pathway in rheumatoid arthritis

Mi Kyung Park, Yang Mi Her, Mi La Cho, Hye Joa Oh, Eun Mi Park, Seung Ki Kwok, Ji Hyeon Ju, Kyung Su Park, Do Sik Min, Ho Youn Kim, Sung Hwan Park

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

Osteoclastogenesis plays an important role in joint destruction in rheumatoid arthritis (RA). IL-15 is a pleiotropic proinflammatory cytokine that appears to help mediate the pathological bone loss. This study was undertaken to explore the signaling molecules essential for osteoclastogenesis mediated by IL-15 in rheumatoid synovial fibroblasts. Expression of phospholipase D1 (PLD1) and osteoclast-related gene expression in synovial tissues and their modulation by treatment with IL-15 and different inhibitors in synovial fibroblasts of RA patients were evaluated using immunohistochemistry and quantitative polymerase chain reaction. The levels of IL-15 in serum and synovial fluid were measured by ELISA. The effects of IL-15 and phosphatidic acid (PA) on osteoclast formation were evaluated in cocultures of rheumatoid synovial fibroblasts and peripheral blood monocytes or monocytes alone in the presence of M-CSF and RANKL. The levels of RANKL and PLD1 but not PLD2 were upregulated significantly by IL-15, and the RANKL level was significantly upregulated by PA in rheumatoid synovial fibroblasts. Blocking PA production with 1-butanol and siRNA against PLD1 significantly inhibited the IL-15-stimulated expression of RANKL and PLD1. IL-15 levels were significantly higher in serum and synovial fluid from patients with RA than in osteoarthritis patients and healthy controls. IL-15 and PA induced osteoclast formation through the mitogen-activated protein kinases (MAPKs) and NF-κB signaling pathways. Activation of PLD1 contributes to IL-15-mediated osteoclastogenesis via the MAPKs and NF-κB signaling pathways in rheumatoid synovial fibroblasts. Our data suggest that PLD1 might be an efficient therapeutic strategy for preventing bone destruction in rheumatoid arthritis.

Original languageEnglish
Pages (from-to)42-51
Number of pages10
JournalImmunology Letters
Volume139
Issue number1-2
DOIs
Publication statusPublished - 2011 Sep 30

    Fingerprint

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

Cite this

Park, M. K., Her, Y. M., Cho, M. L., Oh, H. J., Park, E. M., Kwok, S. K., Ju, J. H., Park, K. S., Min, D. S., Kim, H. Y., & Park, S. H. (2011). IL-15 promotes osteoclastogenesis via the PLD pathway in rheumatoid arthritis. Immunology Letters, 139(1-2), 42-51. https://doi.org/10.1016/j.imlet.2011.04.013