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

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

Research output: Contribution to journalArticlepeer-review

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 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-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.

Original languageEnglish
Pages (from-to)570-573
Number of pages4
JournalEuropean Journal of Immunology
Volume23
Issue number2
Publication statusPublished - Feb 1993

Keywords

  • Cytokines
  • Inflammation
  • Interleukin-1 receptor antagonist
  • Polymorphonuclear cells

ASJC Scopus subject areas

  • Immunology

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