Regulated production of the interferon‐γ‐inducible protein−10 (IP‐10) chemokine by human neutrophils

Abstract

Interferon-γ (IFN-γ)-inducible protein-10 (IP-10), a member of the C-X-C sub-family of chemokines, is known to be produced by monocytes, lymphocytes, keratinocytes and endothelial cells in response to IFN-γ Here, we show that human polymorphonuclear neutrophils (PMN) also have the ability to produce IP-10. IFN-γ alone had a modest effect on IP-10 mRNA accumulation, whereas tumor necrosis factor-α (TNF-α), yeast particles opsonized with IgG (Y-IgG), lipopolysaccharide (LPS), and formyl-methionyl-leucyl-phenylalanine (fMLP) all failed to up-regulate IP-10 gene expression. However, stimulation of neutrophils with IFN-γ in combination with either TNF-α or LPS (but not with Y-IgG or fMLP) resulted in a considerable induction of IP-10 mRNA transcripts, as well as in the extracellular release of the protein. In contrast, the best inducer of IP-10 release from peripheral blood mononuclear cells was IFN-γ alone. Furthermore, mRNA stabilization analyses demonstrated that IP-10 mRNA isolated from PMN stimulated with IFN-γ only, or with IFN-γ plus either TNF-α or LPS, had similar half-lives. Finally, we found that interleukin-10, a known inhibitor of chemokine production in PMN, moderatley suppressed the extracellular production of IP-10 in neutrophils stimulated with IFN-γ plus either LPS or TNF-α. Since IP-10 is a potent chemoattractant for activated T lymphocytes, the ability of neutrophils to produce IP-10 might contribute to the evolution and progression of the inflammatory response.