Interferon-gamma inhibits interleukin-8 production by human polymorphonuclear leucocytes.
Stimulation of human polymorphonuclear leucocytes (PMN) with phagocytosable particles [yeast-IgG (Y-IgG)], lipopolysaccharide (LPS), tumour necrosis factor (TNF) or formyl-methionyl-leucyl-phenyl-alanine (FMLP) results in an increase of the interleukin-8 (IL-8) mRNA accumulation and a subsequent release of the protein. Here, we report that interferon-gamma (IFN-gamma) down-regulates the constitutive IL-8 mRNA levels expressed by resting PMN. As shown by Northern analysis, this down-modulation occurred rapidly, was not dependent on new protein synthesis, and was not caused by an increased rate of degradation of IL-8 mRNA. Preincubation of PMN with IFN-gamma significantly inhibited their ability to release IL-8 upon stimulation with TNF, LPS, FMLP and Y-IgG, but enhanced the respiratory burst capability in response to FMLP and TNF. TNF-, LPS- and FMLP-induced expression of IL-8 mRNA was also selectively inhibited by IFN-gamma. Taken together these findings suggest that IFN-gamma has important regulatory effects on acute inflammatory response because of its capacity to modulate negatively IL-8 gene expression and secretion by human PMN. Further observations revealed that, in human PMN, degradation of IL-8 mRNA is finely regulated, and that cycloheximide (CHX), an inhibitor of protein synthesis, super-induces the mRNA accumulation for IL-8 in a dose- and time-dependent manner.
Cassatella
M A
MA
Institute of General Pathology, University of Verona, Italy.
Guasparri
I
I
Ceska
M
M
Bazzoni
F
F
Rossi
F
F
D001798:Blood Proteins / Q000096:biosynthesis; D015152:Blotting, Northern; D002478:Cells, Cultured; D015870:Gene Expression / Q000502:physiology; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D007371:Interferon-gamma / Q000276:immunology*; D016209:Interleukin-8 / Q000096:biosynthesis* / Q000235:genetics; D008070:Lipopolysaccharides / Q000276:immunology; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000276:immunology; D009504:Neutrophils / Q000276:immunology*; D012333:RNA, Messenger / Q000032:analysis; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology
D001798:Blood Proteins; D007074:Immunoglobulin G; D016209:Interleukin-8; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D009240:N-Formylmethionine Leucyl-Phenylalanine; D007371:Interferon-gamma