Involvement of TNF-like weak inducer of apoptosis in the pathogenesis of collagen-induced arthritis.
TNF-like weak inducer of apoptosis (TWEAK) is a type II membrane protein belonging to the TNF family that regulates apoptotic cell death, cellular proliferation, angiogenesis, and inflammation. However, the role of TWEAK in the pathogenesis of rheumatoid arthritis (RA) remains unclear. In this study, we have investigated the effect of neutralizing anti-TWEAK mAb on the development of collagen-induced arthritis (CIA), a well-established murine model of RA. Administration of anti-TWEAK mAb significantly ameliorated paw swelling, synovial hyperplasia, and infiltration of inflammatory cells. The levels of proinflammatory chemokines such as MCP-1 and MIP-2 in serum and knee joints were reduced by this treatment. Consistently, recombinant TWEAK enhanced the proliferation of MCP-1 and MIP-2 production by synovial cells from CIA mice in vitro. Histological examination also revealed that the treatment with anti-TWEAK mAb suppressed the development of small vessels in synovial tissues. These results indicated anti-inflammatory and antiangiogenic effects of the TWEAK blockade in CIA, which may be also beneficial for the treatment of RA.
Kamata
Koichi
K
Department of Immunology, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan.
Kamijo
Seiji
S
Nakajima
Atsuo
A
Koyanagi
Akemi
A
Kurosawa
Hisashi
H
Yagita
Hideo
H
Okumura
Ko
K
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D017209:Apoptosis; D001169:Arthritis, Experimental / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D049109:Cell Proliferation / Q000187:drug effects; D018932:Chemokine CCL2 / Q000032:analysis / Q000097:blood; D054426:Chemokine CXCL2; D018925:Chemokines / Q000032:analysis / Q000097:blood; D003094:Collagen / Q000633:toxicity; D000074049:Cytokine TWEAK; D007719:Knee Joint / Q000737:chemistry / Q000473:pathology; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D018919:Neovascularization, Physiologic / Q000187:drug effects; D013583:Synovial Membrane / Q000473:pathology; D000079424:Tumor Necrosis Factor Inhibitors; D048069:Tumor Necrosis Factors / Q000378:metabolism* / Q000494:pharmacology
D000911:Antibodies, Monoclonal; C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D054426:Chemokine CXCL2; D018925:Chemokines; C404915:Cxcl2 protein, mouse; D000074049:Cytokine TWEAK; C491645:Tnfsf12 protein, mouse; D000079424:Tumor Necrosis Factor Inhibitors; D048069:Tumor Necrosis Factors; D003094:Collagen