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Expression of interleukin‐1 receptor antagonist (IL‐1ra) by human circulating polymorphonuclear cells

1993; Wiley; Volume: 23; Issue: 2 Linguagem: Inglês

10.1002/eji.1830230242

1521-4141

Fabio Re, Manuela Mengozzi, Marta Muzio, Charles A. Dinarello, Alberto Mantovani, Francesco Colotta,

IL-33, ST2, and ILC Pathways

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 lipopolysaccharrides (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‐1β interferon (IFN)‐γ 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 mRN A 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‐1β IFN‐γ 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.