Transcriptional activation of the interleukin-8 gene by platelet-activating factor in human peripheral blood monocytes.
Interleukin-8 (IL-8) is a member of the chemokine family and a potent neutrophil chemoattractant and activator. It is produced by a variety of cell types during inflammation. In the present work, we examined the regulation of IL-8 gene expression in monocytes by the pro-inflammatory lipid mediator, platelet-activating factor (PAF). Stimulation of human peripheral blood monocytes with PAF augmented their release of IL-8. The enhancement of IL-8 secretion was associated with an increase in IL-8 mRNA expression. PAF induced a concentration- and time-dependent augmentation of IL-8 mRNA accumulation. The response was maximal at PAF concentrations of 10-100 nM. The increased mRNA expression was evident after 1.5 hr of stimulation and persisted for 6 hr. Stimulation of monocytes with PAF, followed by arrest of de novo transcription with actinomycin D, indicated that PAF only marginally increased the stability of IL-8 mRNA. However, in vitro nuclear transcription demonstrated that the enhancement of IL-8 mRNA expression occurred mainly at the transcriptional level. The PAF-induced increase in IL-8 mRNA levels could be blocked with a PAF receptor antagonist. These results show, for the first time, that IL-8 gene expression and protein production can be upregulated by PAF. This interaction could be important in the development and amplification of the inflammatory response.
Denault
S
S
Department of Pediatrics, Faculty of Medicine, Univerśity of Sherbrooke, Quebec, Canada.
April
M J
MJ
Stanková
J
J
D015152:Blotting, Northern; D018929:Cell Culture Techniques; D004306:Dose-Response Relationship, Immunologic; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D016209:Interleukin-8 / Q000235:genetics* / Q000378:metabolism; D009000:Monocytes / Q000276:immunology*; D010972:Platelet Activating Factor / Q000276:immunology*; D010980:Platelet Membrane Glycoproteins / Q000037:antagonists & inhibitors; D012333:RNA, Messenger / Q000235:genetics; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D014158:Transcription, Genetic / Q000276:immunology*
D016209:Interleukin-8; D010972:Platelet Activating Factor; D010980:Platelet Membrane Glycoproteins; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; C039351:platelet activating factor receptor