title: Expression of interleukin-1 receptor antagonist (IL-1ra) by human circulating polymorphonuclear cells.
abstract: After appropriate stimulation, mononuclear phagocytes express a specific inhibitor of interleukin (IL)-1, now re-named IL-1 receptor antagonist (IL-1ra). In this study we have examined the production of IL-1ra by polymorphonuclear cells (PMN). Human PMN isolated from peripheral blood expressed low but detectable levels of IL-1ra transcripts, which were considerably augmented after treatment with lipopolysaccharides (LPS) and cytokines [IL-4, granulocyte (G)- and granulocyte macrophage (GM)-Colony Stimulating factor (CSF), and tumor necrosis factor (TNF)]. The levels of induced IL-1 ra transcripts were comparable to those observed in endotoxin-stimulated human monocytes. By contrast IL-1 beta, interferon (IFN)-gamma and chemotactic factors (fMLP, C5a and IL-8) failed to promote IL-1ra expression in PMN. IL-1ra induction by LPS reached peak levels at 10 ng/ml after 3-6 h and remained sustained 24 h after stimulation. Induction by LPS and GM-CSF appears to be at the transcriptional level, as assessed by inhibiting mRNA synthesis with actinomycin D. Inhibition of protein synthesis by cycloheximide superinduced both basal and inducible IL-1ra mRNA. In addition to expressing mRNA, PMN also produce IL-1ra protein. Secretion of IL-1ra was induced in PMN treated with LPS, IL-4 and GM-CSF, but not by IL-1 beta, IFN-gamma and fMLP, thus yielding results that paralleled those seen in Northern blot experiments. These data indicate that, among myelomonocytic cells, PMN, in addition to mononuclear phagocytes, can express IL-1ra, suggesting that PMN, while exerting a series of pro-inflammatory activities, may also modulate the inflammatory potential of IL-1 in tissues.
authors.affiliation: Centro Daniela e Catullo Borgomainerio, Milano, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Re
authors.forename: M
authors.initials: M
authors.lastname: Mengozzi
authors.forename: M
authors.initials: M
authors.lastname: Muzio
authors.forename: C A
authors.initials: CA
authors.lastname: Dinarello
authors.forename: A
authors.initials: A
authors.lastname: Mantovani
authors.forename: F
authors.initials: F
authors.lastname: Colotta
mesh_terms: D015152:Blotting, Northern; D002478:Cells, Cultured; D002630:Chemotactic Factors / Q000276:immunology; D016207:Cytokines / Q000276:immunology; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1 / Q000276:immunology; D008070:Lipopolysaccharides / Q000276:immunology; D009504:Neutrophils / Q000276:immunology*; D012333:RNA, Messenger / Q000235:genetics; D012795:Sialoglycoproteins / Q000096:biosynthesis*
chemical_list: D002630:Chemotactic Factors; D016207:Cytokines; C507763:IL1RN protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D012795:Sialoglycoproteins