Regulated production of the interferon-gamma-inducible protein-10 (IP-10) chemokine by human neutrophils

Eur J Immunol. 1997 Jan;27(1):111-5. doi: 10.1002/eji.1830270117.


Interferon-gamma (IFN-gamma)-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-gamma. Here, we show that human polymorphonuclear neutrophils (PMN) also have the ability to produce IP-10. IFN-gamma alone had a modest effect on IP-10 mRNA accumulation, whereas tumor necrosis factor-alpha (TNF-alpha), 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-gamma in combination with either TNF-alpha 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-gamma alone. Furthermore, mRNA stabilization analyses demonstrated that IP-10 mRNA isolated from PMN stimulated with IFN-gamma only, or with IFN-gamma plus either TNF-alpha or LPS, had similar half-lives. Finally, we found that interleukin-10, a known inhibitor of chemokine production in PMN, moderately suppressed the extracellular production of IP-10 in neutrophils stimulated with IFN-gamma plus either LPS or TNF-alpha. 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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Cells, Cultured
  • Chemokine CXCL10
  • Chemokines, CXC*
  • Cytokines / biosynthesis*
  • Dactinomycin / pharmacology
  • Gene Expression / drug effects
  • Humans
  • Interferon-gamma / pharmacology
  • Lipopolysaccharides / pharmacology
  • Neutrophils / metabolism*
  • RNA, Messenger / genetics
  • Time Factors


  • Chemokine CXCL10
  • Chemokines, CXC
  • Cytokines
  • Lipopolysaccharides
  • RNA, Messenger
  • Dactinomycin
  • Interferon-gamma