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Oncostatin M Receptor-β Signaling Limits Monocytic Cell Recruitment in Acute Inflammation¹

Emily Hams^*, Chantal S. Colmont^*, Vincent Dioszeghy^*, Victoria J. Hammond^*, Ceri A. Fielding^*, Anwen S. Williams, Minoru Tanaka, Atsushi Miyajima, Philip R. Taylor^*, Nicholas Topley^* and Simon A. Jones^2,*

^* Department of Medical Biochemistry and Immunology and Department of Rheumatology, School of Medicine, Cardiff University, Cardiff, United Kingdom; and Institute of Molecular and Cellular Biosciences, University of Tokyo, Tokyo, Japan

Although the IL-6-related cytokine oncostatin M (OSM) affects processes associated with disease progression, the specific function of OSM in the face of an inflammatory challenge remains unclear. In this report, a peritoneal model of acute inflammation was used to define the influence of OSM on chemokine-mediated leukocyte recruitment. When compared with wild-type and IL-6-deficient mice, peritoneal inflammation in oncostatin M receptor-β-deficient (OSMR-KO) mice resulted in enhanced monocytic cell trafficking. In contrast to IL-6-deficient mice, OSMR-KO mice displayed no difference in neutrophil and lymphocyte migration. Subsequent in vitro studies using human peritoneal mesothelial cells and an in vivo appraisal of inflammatory chemokine expression after peritoneal inflammation identified OSM as a prominent regulator of CCL5 expression. Specifically, OSM inhibited IL-1β-mediated NF-B activity and CCL5 expression in human mesothelial cells. This was substantiated in vivo where peritoneal inflammation in OSMR-KO mice resulted in a temporal increase in both CCL5 secretion and NF-B activation. These findings suggest that IL-6 and OSM individually affect the profile of leukocyte trafficking, and they point to a hitherto unidentified interplay between OSM signaling and the inflammatory activation of NF-B.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported in part by research awards from The Wellcome Trust and Arthritis Research Campaign. E.H. and V.E.H. are respectively funded by a Cardiff University School of Medicine Ph.D. Studentship and a Medical Research Council Capacity Building Studentship. P.R.T. is the recipient of a Medical Research Council Senior Fellowship. C.A.F. is a Kidney Research U.K. Career Development Fellow.

² Address correspondence and reprint requests to Dr. Simon A. Jones, Department of Medical Biochemistry and Immunology, School of Medicine, Tenovus Building, Heath Park, Cardiff University, Cardiff, CF14 4XN, U.K. E-mail address: JonesSA{at}cf.ac.uk

³ Abbreviations used in this paper: OSM, oncostatin M; KO, knockout; OSMR-KO, OSM receptor-β deficient; WT, wild type; HPMC, human peritoneal mesothelial cells; SES, Staphylococcus epidermidis.