Oncostatin M Production and Regulation by Human Polymorphonuclear Neutrophils

Abstract

Oncostatin M (OSM) is an interleukin-6 (IL-6) family cytokine known in particular to induce the synthesis of acute-phase proteins by hepatocytes. Because human polymorphonuclear neutrophils (PMN) can secrete numerous cytokines, the potential production of OSM by PMN was investigated. Highly purified PMN were found to contain an intracellular stock of preformed OSM that was rapidly mobilized by degranulating agents such as phorbol myristate acetate and granulocyte-macrophage colony-stimulating factor (GM-CSF). Moreover, PMN produced OSM after a few hours of stimulation by various agonists. The most potent effect was observed with the combination of lipopolysaccharide and GM-CSF, which had a concentration- and time-dependent effect at both the protein and mRNA levels. Actinomycin D strongly reduced OSM mRNA induction, suggesting the involvement of gene transcription. Cycloheximide inhibited OSM protein synthesis but did not affect the release of preformed stores. In addition, OSM production was downregulated by dexamethasone, whereas IL-10 had no effect. The OSM produced by PMN was biologically active, as demonstrated by its ability to induce 1-acid glycoprotein synthesis by HepG2 cells. OSM secretion thus occurs through a two-step mechanism in PMN, consisting of early release of a preformed stock, followed by de novo protein synthesis. This would allow rapid and sustained OSM release to occur at inflammatory sites, and may contribute to the modulation of local inflammation.

Expression of oncostatin M in hematopoietic organs

“…4D,E, inset, arrowheads). Grenier et al (1999, 2001) showed that human blood PMNs were able to release OSM in the inflammatory response. In contrast to PMNs, almost all eosinophils in human are distributed in the mucosal tissues not in the circulation (Weller, 1991; Matthews et al, 1998).…”

“…Northern blot analysis revealed that OSM mRNA was expressed at the highest level in the bone marrow, predominantly in thymus, but not in spleen, small intestine, lung, or liver of adult mice (Yoshimura et al, 1996). Although circulating polymorphonuclear neutrophils (PMNs) are shown to produce OSM (Grenier et al, 1999), the localization of OSM mRNA in hematopoietic organs remains unclear. To examine which cells express OSM in the hematopoietic organs during murine embryogenesis and in the adult mice, we used in situ hybridization techniques and immunohistochemical methods.…”

Oncostatin M synergises with house dust mite proteases to induce the production of PGE2 from cultured lung epithelial cells

“…We also showed that OSM alone induced the release of GM‐CSF from epithelial cells, suggesting an interaction between these cytokines. Indeed, GM‐CSF has been shown to induce the release of OSM from neutrophils ( Grenier et al ., 1999 ), suggesting that a positive feedback reaction may occur within the context of allergic inflammation.…”

Oncostatin M: an interleukin‐6‐like cytokine relevant to airway remodelling and the pathogenesis of asthma

“…OSM is produced in cell types that are known to increase in number and activity in asthma, including monocytes and macrophages, activated T cells and neutrophils [17, 30, 31]. More recently, it has also been demonstrated that OSM is produced by dendritic cells [32].…”