Interleukin-27 suppresses osteoclastogenesis via induction of interferon-γ.
Interleukin (IL)-27 is a heterodimeric cytokine that is known to have both stimulatory and inhibitory functions during immune responses. We investigated the effects of IL-27 on arthritis and bone erosion in the murine collagen-induced arthritis (CIA) model. We demonstrate that the inhibitory effect of IL-27 on osteoclastogenesis is associated with interferon-γ (IFN-γ) production by using an IFN-γ knockout mouse model. The IL-27-Fc was injected into both CIA and IFN-γ-deficient mice. The effects of IL-27-Fc on osteoclast differentiation were evaluated both in vitro and in vivo. The IL-27-Fc-injected mice showed significantly lower arthritis indices and fewer tartrate-resistant acid-phosphatase-positive osteoclasts in their joint tissues than untreated mice. Interleukin-27 inhibited osteoclastogenesis from bone marrow-derived mononuclear cells in vitro, which was counteracted by the addition of anti-IFN-γ antibody. The IL-27-Fc did not affect arthritis in IFN-γ knockout mice. Interleukin-27 also suppressed osteoclast differentiation in human and intriguingly, it could promote the expression of IFN-γ on priming osteoclasts. These results imply that IL-27 suppressed the generation of CIA and osteoclastogenesis, which were mediated by the induction of IFN-γ.
The Rheumatism Research Centre, Catholic Research Institute of Medical Science, The Catholic University of Korea, Seoul, South Korea.
Jin-Sil
JS
Park
Young Ok
YO
Jung
Hye-Joa
HJ
Oh
Seong Jeong
SJ
Park
Yu-Jung
YJ
Heo
Chang-Min
CM
Kang
Seung-Ki
SK
Kwok
Ji Hyeon
JH
Ju
Kyung Su
KS
Park
Mi-La
ML
Cho
Young-Chul
YC
Sung
Sung-Hwan
SH
Park
Ho-Youn
HY
Kim
D000818:Animals; D001169:Arthritis, Experimental / Q000209:etiology; D002454:Cell Differentiation / Q000187:drug effects; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis* / Q000276:immunology; D020381:Interleukin-17 / Q000276:immunology / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D010010:Osteoclasts / Q000187:drug effects* / Q000502:physiology; D010012:Osteogenesis / Q000187:drug effects*
D020381:Interleukin-17; D007371:Interferon-gamma