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Blood, Vol. 93 No. 4 (February 15), 1999:
pp. 1413-1421
Oncostatin M Production and Regulation by Human Polymorphonuclear
Neutrophils
Alain Grenier,
Monique Dehoux,
Anne Boutten,
Montserrat Arce-Vicioso,
Geneviève Durand,
Marie-Anne Gougerot-Pocidalo, and
Sylvie Chollet-Martin
From the Laboratoire de Biochimie, Hôpital de Montfermeil,
Montfermeil, France; the Laboratoire de Biochimie, INSERM U 408, Laboratoire d'Hématologie et d'Immunologie et INSERM U 479, Hôpital Bichat, Paris, France; and the Laboratoire de Biochimie,
Faculté de Pharmacie, Chatenay-Malabry, France.
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.
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