Oncostatin M receptor-beta signaling limits monocytic cell recruitment in acute inflammation.
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-beta-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-1beta-mediated NF-kappaB 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-kappaB 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-kappaB.
Hams
Emily
E
Department of Medical Biochemistry and Immunology, Cardiff University, Cardiff, United Kingdom.
Colmont
Chantal S
CS
Dioszeghy
Vincent
V
Hammond
Victoria J
VJ
Fielding
Ceri A
CA
Williams
Anwen S
AS
Tanaka
Minoru
M
Miyajima
Atsushi
A
Taylor
Philip R
PR
Topley
Nicholas
N
Jones
Simon A
SA
D000208:Acute Disease; D000818:Animals; D002465:Cell Movement / Q000276:immunology*; D002478:Cells, Cultured; D018925:Chemokines / Q000235:genetics / Q000276:immunology; D005786:Gene Expression Regulation / Q000276:immunology; D006801:Humans; D007249:Inflammation / Q000276:immunology / Q000378:metabolism; D008024:Ligands; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009000:Monocytes / Q000166:cytology* / Q000276:immunology / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism; D053681:Oncostatin M Receptor beta Subunit / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000276:immunology*
D018925:Chemokines; D008024:Ligands; D016328:NF-kappa B; D053681:Oncostatin M Receptor beta Subunit