The regulation of CXCR4 and CCR5 expression on human monocytes by Th1 and Th2 cytokines: Functional implications on cell migration and HIV infection.

Abstract

The role of Th1 (IL,-2 and IFN-gamma) and Th2 (IL-4 and IL-13) cytokines in the regulation of CXCR4 and CCR5 expression by monocytes, and the functional implications of Th1 and Th2 cytokine induced alterations in chemokine receptor expression on chemotaxis and HIV infection, are poorly understood and constituted the major aim of this investigation. To understand the molecular mechanisms of chemokine receptor down regulation induced by Th1 and Th2 cytokines, the expression of mRNA encoding CXCR4 and CCR5 was examined. The functional consequences of decreases in CXCR4 and CCR5 expression by Th1 and Th2 cytokines were investigated by chemotactic assays. Monocytes from HIV negative adults, HIV positive adults, and HIV negative cord blood were cultured in the presence and absence of Th1 (IL-2 and IFN-gamma) and Th2 (IL-4 and IL-13) cytokines before their ability to migrate in response to the CXCR4 ligand SDF-1, and the CCR5 ligand MIP-1alpha, were measured. The consequences of decreases in CXCR4 and CCR5 expression by Th1 and Th2 cytokines were also investigated with respect to HIV entry and replication. (Abstract shortened by UMI.)