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Reciprocal cross-talk between RANKL and interferon-gamma-inducible protein 10 is responsible for bone-erosive experimental arthritis

Cited 71 time in Web of Science Cited 80 time in Scopus
Authors
Kwak, Han Bok; Ha, Hyunil; Kim, Ha-Neui; Lee, Jong-Ho; Kim, Hun Soo; Lee, Seungbok; Kim, Hyun-Man; Kim, Jung Yeon; Kim, Hong-Hee; Song, Yeong Wook; Lee, Zang Hee
Issue Date
2008-04-29
Publisher
American College of Rheumatology
Citation
Arthritis Rheum. 2008 ;58(5):1332-42.
Keywords
AnimalsArthritis, Rheumatoid/*etiology/immunologyCells, CulturedChemokine CXCL10/*physiologyMiceMice, Inbred DBARANK Ligand/*physiology
Abstract
OBJECTIVE: Interferon-gamma-inducible protein 10 (IP-10; also called CXCL10), a chemokine important in the migration and proliferation of T cells, is induced in a wide variety of cell types. However, the role of IP-10 in rheumatoid arthritis (RA) remains largely unknown. The purpose of this study was to examine the potential role of IP-10 in bone resorption and RA through examination of a mouse model of collagen-induced arthritis (CIA). METHODS: The effects of IP-10 on mouse T cells during osteoclast differentiation were examined in migration assays. The bone-erosive activity of IP-10 was determined in vivo in a mouse model of CIA by histologic and immunostaining analyses. Cytokine levels in serum and culture medium were measured with sandwich enzyme-linked immunosorbent assays. RESULTS: Serum concentrations of IP-10 were significantly higher in mice with CIA than in control mice. RANKL greatly induced IP-10 expression in osteoclast precursors, but not in mature osteoclasts. IP-10 stimulated the expression of RANKL and tumor necrosis factor alpha (TNFalpha) in CD4+ T cells and induced osteoclastogenesis in cocultures of CD4+ T cells and osteoclast precursors. However, IP-10 did not induce RANKL or TNFalpha in CD8+ T cells. Treatment with neutralizing antibody to IP-10 significantly inhibited the infiltration of CD4+ T cells and F4/80+ macrophages into the synovium and attenuated bone destruction in mice with CIA. Furthermore, levels of RANKL and TNFalpha were inhibited by antibody to IP-10. Bone erosion was observed in mice infected with an IP-10 retrovirus. CONCLUSION: Our findings suggest that IP-10 plays a critical role in the infiltration of CD4+ T cells and F4/80+ macrophages into inflamed joints and causes bone destruction. Our results provide the first evidence that IP-10 contributes to the recruitment of inflammatory cells and is involved in bone erosion in inflamed joints.
ISSN
0004-3591 (Print)
Language
English
URI
https://hdl.handle.net/10371/62238
DOI
https://doi.org/10.1002/art.23372
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College of Medicine/School of Medicine (의과대학/대학원)Internal Medicine (내과학전공)Journal Papers (저널논문_내과학전공)
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