期刊
JOURNAL OF LEUKOCYTE BIOLOGY
卷 93, 期 5, 页码 751-759出版社
FEDERATION AMER SOC EXP BIOL
DOI: 10.1189/jlb.0912473
关键词
macrophage; inflammation; cytokine; IgG Fc receptor; oste oclastogenesis
资金
- American College of Rheumatology
- U.S. National Institutes of Health [AR055240, AR050250, AR054796, AI092490, HL108795, AR048697]
- NATIONAL CANCER INSTITUTE [P30CA060553] Funding Source: NIH RePORTER
- NATIONAL HEART, LUNG, AND BLOOD INSTITUTE [P01HL108795] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES [R21AI092490] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES [R01AR050250, R01AR048697, R01AR054796, R01AR055240] Funding Source: NIH RePORTER
RA is a chronic inflammatory disease characterized by the persistent expression of inflammatory cytokines from macrophages, which may be mediated, in part, through TLR2 signaling. Earlier studies demonstrate a role for TLR2 signaling in dampening the arthritis in IL-1Ra(-/-) mice, which was mediated through T cells. This study was performed to determine whether TLR2 signaling plays a role in the pathogenesis of T cell-independent arthritis triggered by transferring serum from K/BxN mice. We documented more severe arthritis in Tlr2(-/-) mice compared with WT controls. The Tlr2(-/-) mice also demonstrated increased inflammation, erosion, pannus formation, and osteoclastogenesis, as well as increased IL-1 beta and decreased IL-10 within the joints. In vitro bone marrow-differentiated macrophages expressed comparable levels of activating and inhibitory Fc gamma Rs, however when stimulated with immune complexes, the Tlr2(-/-) macrophages expressed decreased IL-10 and reduced activation of Akt and ERK. Our findings indicate that Tlr2(-/-) promotes the effector phase of arthritis through decreased IL-10 by macrophages, which is important, not only as an anti-inflammatory cytokine but also in restraining the differentiation and activation of osteoclasts.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据