Modulation of formyl peptide receptor expression by IL-10 in human monocytes and neutrophils.
IL-10, originally described as a cytokine synthesis inhibitory factor, is secreted by a number of cells of the immune system, including monocytes and T cells. Although IL-10 is being assigned as an immunosuppressive cytokine, our study showed that FMLP-R mRNA was rapidly up-regulated by exposure of monocytes to graded concentrations of this cytokine, with maximal (three- to fourfold) stimulation with 10 ng/ml. The effect was rapid, being observable as early as 1 h of treatment with IL-10, maximal between 2 and 4 h, and still evident after 24 h and was associated with an increase of receptor expression on the cell surface as assessed by flow cytometry analysis. Pretreatment of monocytes with actinomycin D completely abrogated the effect of IL-10, suggesting a transcriptional regulation. Moreover, IL-10-treated monocytes showed a significantly enhanced functional responsiveness to FMLP with enhanced (three- to fourfold) chemotaxis and augmented (twofold) intracellular calcium mobilization. In polymorphonuclear neutrophils (PMN), IL-10 also mediated a twofold augmentation of FMLP-R expression. In parallel experiments, we observed that IL-10 could differentially modulate other chemotactic receptors. Hence, we observed that IL-10 augmented two-to threefold platelet-activating factor receptor (PAF-R) expression, whereas it had no significant effect on the fifth component of complement (C5a) receptor (C5a-R) expression. Collectively, our results demonstrate that IL-10 may play an important role in inflammatory process through modulation of chemotactic receptor expression.
Thivierge
M
M
Department of Pediatrics, Faculty of Medicine, Université de Sherbrooke, Québec, Canada.
Parent
J L
JL
Stankova
J
J
Rola-Pleszczynski
M
M
D002634:Chemotaxis, Leukocyte / Q000276:immunology; D005786:Gene Expression Regulation / Q000276:immunology; D006801:Humans; D016753:Interleukin-10 / Q000502:physiology*; D009000:Monocytes / Q000276:immunology / Q000378:metabolism* / Q000502:physiology; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000378:metabolism* / Q000494:pharmacology; D009504:Neutrophils / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D044042:Receptors, Formyl Peptide; D011971:Receptors, Immunologic / Q000096:biosynthesis* / Q000235:genetics; D018000:Receptors, Peptide / Q000096:biosynthesis* / Q000235:genetics; D014158:Transcription, Genetic / Q000276:immunology; D015854:Up-Regulation / Q000276:immunology
D012333:RNA, Messenger; D044042:Receptors, Formyl Peptide; D011971:Receptors, Immunologic; D018000:Receptors, Peptide; D016753:Interleukin-10; D009240:N-Formylmethionine Leucyl-Phenylalanine