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 s ecreted 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- t o fourfold) stimulation with 10 ng/ml, The effect was rapid, being observab le 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 ex pression on the cell surface as assessed by flow cytometry analysis. Pretre atment of monocytes with actinomycin D completely abrogated the effect of I L-10, suggesting a transcriptional regulation. Moreover, IL-10-treated mono cytes showed a significantly enhanced functional responsiveness to FMLP wit h enhanced (three- to fourfold) chemotaxis and augmented (twofold) intracel lular calcium mobilization. In polymorphonuclear neutrophils (PNN), IL-10 a lso mediated a twofold augmentation of FMLP-R expression. In parallel exper iments, we observed that IL-10 could differentially modulate other chemotac tic receptors. Hence, we observed that IL-10 augmented two- to threefold pl atelet-activating factor receptor (PAF-R) expression, whereas it had no sig nificant effect on the fifth component of complement (C5a) receptor (C5a-R) expression. Collectively, our results demonstrate that IL-10 may play an i mportant role in inflammatory processes through modulation of chemotactic r eceptor expression.