Tumor necrosis factor alpha induces upregulation of CXC-chemokine receptor type II expression and magnifies the proliferative activity of CXC-chemokines in human melanocytes.

The CXC-chemokines Groalpha and interleukin-8 (IL-8) are ligands for two different G protein-coupled receptors, named CXC-chemokine receptor I & II (CXCRI & II). Both cytokines are potent growth factors for human melanoma cells, with only limited proliferative activity towards normal melanocytes. Here we analysed the influence of various cytokines on the expression of CXCRI & II and the CXC-chemokine-induced proliferation in human melanocytes. Flow cytometric studies revealed no protein expression of CXCRI and low protein expression of CXCRII at the cell surface of normal melanocytes. Tumor necrosis factor alpha (TNFalpha) enhanced the mRNA and protein expression of CXCRII, but did not influence expression of CXCRI. A consequence of TNFalpha-pretreatment of human melanocytes was a significant enhancement of the proliferative activity of IL-8 and Groalpha. This study implicates that TNFalpha magnifies the biological activity of CXC-chemokines in melanocytes by induction of CXCRII expression.