Involvement of retinoic acid-inducible gene-I in inflammation of rheumatoid fibroblast-like synoviocytes.
Interferon (IFN)-gamma is a major cytokine that regulates T helper 1-type immune reactions and serves as an important mediator in the pathogenesis of autoimmune diseases. Retinoic acid-inducible gene-I (RIG-I) is an IFN-gamma-inducible gene and known to be involved in the inflammatory and immune reactions. In the present study, we found high levels of RIG-I expression in synovial tissues of rheumatoid arthritis (RA), while the expression in osteoarthritis tissues was low. Treatment of cultured fibroblast-like synoviocytes with IFN-gamma markedly induced the expression of RIG-I. Knockdown of RIG-I in fibroblast-like synoviocytes, with specific siRNA, resulted in the inhibition of the IFN-gamma-induced expression of chemokine (C-X-C motif) ligand 10 (CXCL10)/IFN-gamma-inducible protein-10 (IP-10), a chemokine with chemotactic activity towards T cells. These findings suggest that RIG-I may play an important role in the pathogenesis of synovial inflammation in RA, at least in part, by regulating the IFN-gamma-induced expression of CXCL10/IP-10.
Imaizumi
T
T
Departments of Vascular Biology, Hirosaki University Graduate School of Medicine, Hirosaki, Japan. timaizum@cc.hirosaki-u.ac.jp
Arikawa
T
T
Sato
T
T
Uesato
R
R
Matsumiya
T
T
Yoshida
H
H
Ueno
M
M
Yamasaki
S
S
Nakajima
T
T
Hirashima
M
M
Sakata
K
K
Ishibashi
Y
Y
Toh
S
S
Ohyama
C
C
Satoh
K
K
D001172:Arthritis, Rheumatoid / Q000276:immunology* / Q000378:metabolism; D002478:Cells, Cultured; D054357:Chemokine CXCL10 / Q000378:metabolism; D002634:Chemotaxis, Leukocyte; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases / Q000032:analysis / Q000235:genetics*; D005347:Fibroblasts / Q000276:immunology / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D007150:Immunohistochemistry; D007371:Interferon-gamma / Q000494:pharmacology; D010003:Osteoarthritis / Q000276:immunology; D034622:RNA Interference; D012333:RNA, Messenger / Q000032:analysis; D034741:RNA, Small Interfering / Q000494:pharmacology; D011971:Receptors, Immunologic; D013583:Synovial Membrane / Q000276:immunology* / Q000378:metabolism
D054357:Chemokine CXCL10; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D011971:Receptors, Immunologic; D007371:Interferon-gamma; C452820:RIGI protein, human; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases