Evidence of involvement of CXC-chemokines in proliferation of cultivated human melanocytes.

The CXC-chemokines 1 and 8 (CXCL1 and CXCL8) are ligands for the G protein-coupled CXC-chemokine receptor 2 (CXCR2). Both chemokines and CXCR2 are components of a potent autocrine growth factor loop in human melanoma cells. Currently, expression and biological function of both chemokines in normal human melanocytes is poorly defined. Here we describe that cocktails of melanocyte growth factors consisting of basic fibroblast growth factor (bFGF), endothelin 1 (ET-1) and alpha-melanocyte-stimulating hormone (alpha-MSH) stimulated release of CXCL1 and CXCL8, but did not influence expression of CXCR2 in human melanocytes. Cell studies revealed that CXCL1 and CXCL8 potentiate the proliferative activity of various combinations of cocktails with growth factor such as bFGF, ET-1 and alpha-MSH. Moreover, ligand blocking anti-CXCR2 antibodies reduced proliferation of melanocytes after stimulation with bFGF, ET-1 and alpha-MSH. This study implicates that CXCL1, CXCL8 and their receptor CXCR2 are components of an autocrine mechanism in proliferating human melanocytes.