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Urocortin Expression in Synovium of Patients with Rheumatoid Arthritis and Osteoarthritis: Relation to Inflammatory Activity

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 proinflammatory agent. Urocortin is a new member of the CRH family that acts through the family of CRH receptors. In this study, we demonstrated that the expression of urocortin mRNA in synovia of patients with rheumatoid arthritis was greater than that of patients with osteoarthritis. Also, we detected urocortin and CRH receptor immunoreactivity in the synovial lining cell layer, subsynovial stromal cells, blood vessel endothelial cells, and mononuclear inflammatory cells from the joints of rheumatoid arthritis and osteoarthritis patients. The expression of immunoreactive urocortin was significantly greater in rheumatoid arthritis than osteoarthritis (P < 0.0001) and correlated with the extent of inflammatory infiltrate. CRH receptor immunoreactivity was strong in mononuclear inflammatory cells of rheumatoid arthritis synovia. Urocortin stimulated IL-1ß and IL-6 secretion by human peripheral blood mononuclear cells in vitro. These findings suggest that, like CRH, urocortin is present in peripheral inflammatory sites, such as rheumatoid synovium, and acts as an immune-inflammatory mediator.

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