Journal
JOURNAL OF LEUKOCYTE BIOLOGY
Volume 93, Issue 5, Pages 751-759Publisher
FEDERATION AMER SOC EXP BIOL
DOI: 10.1189/jlb.0912473
Keywords
macrophage; inflammation; cytokine; IgG Fc receptor; oste oclastogenesis
Categories
Funding
- 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
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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.
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