Recombinant IFN-alpha (2b) increases the expression of apoptosis receptor CD95 and chemokine receptors CCR1 and CCR3 in monocytoid cells

IFN-alpha-2b, known as potent immune modulator, can either inhibit or enhan ce immune cell activity within the tightly regulated microenvironment of in flammation, depending upon the concentration of the cytokine and the activa tion stage of the cell. Chemokine receptors, which not only mediate chemota xis of immune cells to the site of inflammation but also affect cellular ac tivation by transferring corresponding signals, represent yet another level of immune regulation. Here we demonstrate that IFN-alpha increases the exp ression of CCR1 and CCR3 in primary mononuclear phagocytes, as well as in t he monocytoid cell line U937, Enhanced receptor mRNA expression correlated with functional readouts such as increased intracellular calcium mobilizati on and cell migration in response to ligands, Expression of CCR2b, CCR4, CC R5, and CXCR4 was unchanged or decreased after IFN-alpha treatment. These o bservations indicate a differentially regulated cellular signaling relation ship of IFN-alpha pathways and chemokine receptor expression. We also provi de evidence that, under these conditions, IFN-alpha treatment increased the expression of CD95 (Fas, Apo1), resulting in enhanced susceptibility to ap optosis, Taken together, these data add important information for the ratio nal application of IFN-alpha (2b) in immune and cancer therapies.