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Interferon-gamma inhibits interleukin-8 production by human polymorphonuclear leucocytes
M A Cassatella1, I Guasparri, M Ceska
1Institute of General Pathology, University of Verona, Italy.
Immunology
|February 1, 1993
Summary
Interferon-gamma (IFN-gamma) reduces interleukin-8 (IL-8) mRNA and protein in human immune cells. This modulation impacts the acute inflammatory response by decreasing IL-8 gene expression and secretion.
Area of Science:
- Immunology
- Molecular Biology
Background:
- Human polymorphonuclear leucocytes (PMN) release interleukin-8 (IL-8) upon stimulation.
- IL-8 plays a key role in acute inflammatory responses.
Purpose of the Study:
- To investigate the effect of interferon-gamma (IFN-gamma) on IL-8 gene expression and secretion in human PMN.
- To understand IFN-gamma's regulatory role in acute inflammation.
Main Methods:
- Northern analysis to assess IL-8 mRNA levels.
- Incubation of PMN with IFN-gamma and various stimuli (Y-IgG, LPS, TNF, FMLP).
- Measurement of IL-8 release and respiratory burst activity.
Main Results:
- IFN-gamma rapidly down-regulates constitutive IL-8 mRNA levels in resting PMN.
- IFN-gamma inhibits IL-8 release induced by TNF, LPS, FMLP, and Y-IgG.
- IFN-gamma enhances PMN respiratory burst activity in response to FMLP and TNF.
- IFN-gamma selectively inhibits TNF-, LPS-, and FMLP-induced IL-8 mRNA expression.
- Cycloheximide (CHX) super-induces IL-8 mRNA accumulation, indicating regulated degradation.
Conclusions:
- IFN-gamma negatively modulates IL-8 gene expression and secretion in human PMN.
- IFN-gamma plays a significant regulatory role in acute inflammatory responses.
- IL-8 mRNA degradation is tightly regulated in human PMN.