A novel mechanism for the regulation of IFN-gamma inducible protein-10 expression in rheumatoid arthritis.
Chemokines play an essential role in the progression of rheumatoid arthritis (RA). In the present study we examined the expression and regulatory mechanisms of IFN-gamma inducible protein (IP)-10 in RA synovitis. RA synovial fluid contained greater amounts of IP-10 than did synovial fluid from patients with osteoarthritis. Immunolocalization analysis indicated that IP-10 was associated mainly with infiltrating macrophage-like cells, and fibroblast-like cells in the RA synovium. The interaction of activated leukocytes with fibroblast-like synoviocytes resulted in marked increases in IP-10 expression and secretion. Moreover, induction of IP-10 was mediated via specific adhesion molecules, as indicated by the finding that both anti-integrin (CD11b and CD18) and intercellular adhesion molecule-1 antibodies significantly inhibited IP-10 induction. These results suggest that IP-10 expression within inflamed joints appears to be regulated not only by inflammatory cytokines but also by the physical interaction of activated leukocytes with fibroblast-like synoviocytes, and that IP-10 may contribute to the recruitment of specific subpopulations of T cells (Th1 type) from the bloodstream into the synovial joints.
Hanaoka
Ryosuke
R
Division of Rheumatology and Clinical Immunology, First Department of Internal Medicine, Showa University School of Medicine, Tokyo, Japan.
Kasama
Tsuyoshi
T
Muramatsu
Mizuho
M
Yajima
Nobuyuki
N
Shiozawa
Fumitaka
F
Miwa
Yusuke
Y
Negishi
Masao
M
Ide
Hirotsugu
H
Miyaoka
Hideyo
H
Uchida
Hitoshi
H
Adachi
Mitsuru
M
D000368:Aged; D001172:Arthritis, Rheumatoid / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D002450:Cell Communication; D002478:Cells, Cultured; D054357:Chemokine CXCL10; D019743:Chemokines, CXC / Q000096:biosynthesis* / Q000235:genetics; D018920:Coculture Techniques; D005260:Female; D005347:Fibroblasts / Q000502:physiology; D005786:Gene Expression Regulation; D006801:Humans; D016023:Integrins / Q000378:metabolism; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D007962:Leukocytes / Q000166:cytology / Q000276:immunology; D008297:Male; D008875:Middle Aged; D013582:Synovial Fluid / Q000276:immunology; D013583:Synovial Membrane / Q000166:cytology; D015854:Up-Regulation
D054357:Chemokine CXCL10; D019743:Chemokines, CXC; D016023:Integrins; D018799:Intercellular Adhesion Molecule-1