Urocortin Expression in Synovium of Patients with Rheumatoid Arthritis and Osteoarthritis: Relation to Inflammatory Activity
Masataka Kohno,
Yutaka Kawahito,
Yasunori Tsubouchi,
Akira Hashiramoto,
Ryoji Yamada,
Ken-ichiro Inoue,
Yoshiaki Kusaka,
Toshikazu Kubo,
Ilia J. Elenkov,
George P. Chrousos,
Motoharu Kondo and
Hajime Sano
First Department of Internal Medicine (Ma.K., Yu.K., Y.T., A.H.,
R.Y., K.-I.I., Mo.K., H.S.) and Department of Orthopedics (Yo.K.,
T.K.), Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan;
Arthritis and Rheumatism Branch (I.J.E.), National Institute of
Arthritis and Musculoskeletal and Skin Diseases, Bethesda, Maryland
20892; and Developmental Endocrinology Branch (G.P.C.), National
Institute of Child Health and Human Development, National Institutes of
Health, Bethesda, Maryland 20892
Address all correspondence and requests for reprints to: Hajime Sano, M.D., Ph.D., Kyoto Perfectural University of Medicine, First Department of Internal Medicine, 465 Kajii-Cho, Kawaramachi-Hirokoji, Kamigyo-Ku, Kyoto, Japan 602-8566. E-mail: hsano{at}koto.kpu-m.ac.jp
Abstract
Peripherally produced CRH acts as a local auto/paracrine
proinflammatoryagent. Urocortin is a new member of the CRH family that
actsthrough the family of CRH receptors. In this study, we
demonstratedthat the expression of urocortin mRNA in synovia of
patientswith rheumatoid arthritis was greater than that of patients
withosteoarthritis. Also, we detected urocortin and CRH receptor
immunoreactivityin the synovial lining cell layer, subsynovial stromal
cells,blood vessel endothelial cells, and mononuclear inflammatory
cellsfrom the joints of rheumatoid arthritis and osteoarthritis
patients.The expression of immunoreactive urocortin was significantly
greaterin rheumatoid arthritis than osteoarthritis
(P < 0.0001)and correlated with the extent of
inflammatory infiltrate. CRHreceptor immunoreactivity was strong in
mononuclear inflammatorycells of rheumatoid arthritis synovia.
Urocortin stimulatedIL-1ß and IL-6 secretion by human peripheral
bloodmononuclear cells in vitro. These findings suggest
that, likeCRH, urocortin is present in peripheral inflammatory sites,
suchas rheumatoid synovium, and acts as an immune-inflammatory
mediator.
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