Abstract
Oncostatin M (OSM) is a pleiotropic cytokine of the IL-6 family and displays both pro-inflammatory and anti-inflammatory activities. We studied the impact of OSM on the gene activation profile of human synovial cells, which play a central role in the progression of inflammatory responses in joints. In synovial cells stimulated with lipopolysaccharide and recombinant human granulocyte-macrophage colony-stimulating factor, recombinant human OSM and native OSM secreted by human granulocytes both reduced the gene expression and secretion of IL-1β and CXCL8, but increased that of IL-6 and CCL2. This impact on synovial cell activation was not obtained using IL-6 or leukaemia inhibitory factor. Signal transducer and activator of transcription-1 appeared to mediate the effects of OSM on stimulated human synovial fibroblasts. In the murine dorsal air pouch model of inflammation, OSM reduced the expression of the pro-inflammatory cytokines IL-1β and TNF-α in lining tissues, and their presence in the cavity. These results as a whole suggest an anti-inflammatory role for OSM, guiding inflammatory processes towards resolution.
Highlights
Oncostatin M is a pleiotropic cytokine associated with haematopoiesis, development, tissue remodelling and inflammation [1]
ELISA kits for human IL-1, human CXCL8, murine TNF-␣, murine IL-1 were obtained from Biolegend (San Diego, CA, USA) kits for human and murine IL-6 were obtained from Biosource Invitrogen (Carlsbad, CA, USA) and the kit for human Oncostatin M (OSM) was obtained from Antigenix America Inc. (Huntington Station, NY, USA)
We observed in this study that recombinant as well as native OSM decreased the release of IL-1 from activated human primary synovial fibroblasts (HSFs)
Summary
Oncostatin M is a pleiotropic cytokine associated with haematopoiesis, development, tissue remodelling and inflammation [1]. Oncostatin M is structurally and functionally related to other members of the IL-6 family, such as IL-6, IL-11 and leukaemia inhibitory factor (LIF), all of which perform their signalling function via the common transducing receptor chain glycoprotein gp130 [2, 3]. Human OSM has the exceptional capability of engaging two different receptor complexes. Numerous cell types participate in the pathogenesis of inflammatory diseases. Polymorphonuclear neutrophils (PMNs), which play important roles in the early stages of inflammation, are often the first and most abundant cell type to migrate to injury sites and recognized as a major source of OSM [14, 21]. Polymorphonuclear neutrophils and OSM are both found in increased amounts in the doi:10.1111/j.1582-4934.2011.01412.x
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