IL-10 up-regulates CCR5 gene expression in human monocytes.
The chemokine receptor CCR5 has been found to play a key role in early infection with macrophage-tropic isolates of HIV-1 and CCR5 deficiency is associated with a relative resistance to HIV-1 infection. In this context, we studied the regulation of CCR5 gene expression by cytokines, and in particular, interleukin (IL)-10 in human monocytes. CCR5 mRNA was rapidly up-regulated by exposure of monocytes to graded concentrations of IL-10, with near maximal stimulation with 10 ng/ml. The effect was rapid, being detectable as early as 1 h and maximal between 2 and 4 h of treatment. Pretreatment of monocytes with actinomycin D prevented the IL-10-induced effect, suggesting a transcriptional mechanism for CCR5 up-regulation by IL-10. Protein expression of CCR5 was also enhanced by IL-10, as indicated by a 3-fold increase in anti-CCR5 antibody labeling of monocytes treated for 20 h with IL-10. Increased surface expression of CCR5 persisted at 48 h of treatment. Moreover, IL-10-treated monocytes responded with augmented intracellular Ca++ mobilization and enhanced (3-4-fold) chemotaxis in response to the CCR5 ligand MIP-1beta(25 ng/ml). Taken together, our data indicate that IL-10 can modulate CCR5 expression and function. This can constitute a potentially important regulatory mechanism which can affect not only responses during inflammation, but also susceptibility to HIV-1 infection.
Department of Pediatrics Faculty of Medicine, Université de Sherbrooke, Quebec, Canada.
M
M
Houle
M
M
Thivierge
C
C
Le Gouill
J
J
Stankovà
M
M
Rola-Pleszczynski
D000911:Antibodies, Monoclonal / Q000378:metabolism; D002478:Cells, Cultured; D054407:Chemokine CCL4; D004306:Dose-Response Relationship, Immunologic; D005434:Flow Cytometry; D005786:Gene Expression Regulation / Q000276:immunology*; D006801:Humans; D016753:Interleukin-10 / Q000502:physiology*; D019402:Macrophage Inflammatory Proteins / Q000494:pharmacology; D009000:Monocytes / Q000276:immunology / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D019713:Receptors, CCR5 / Q000096:biosynthesis* / Q000235:genetics*; D013997:Time Factors; D015854:Up-Regulation / Q000276:immunology*
D000911:Antibodies, Monoclonal; D054407:Chemokine CCL4; D019402:Macrophage Inflammatory Proteins; D012333:RNA, Messenger; D019713:Receptors, CCR5; D016753:Interleukin-10