Mockenhaupt Maja, Peters Frank, Schwenk-Davoine Ildiko, Herouy Yared, Schraufstätter Ingrid, Elsner Peter, Norgauer Johannes
Department of Experimental Dermatology, University of Freiburg, Hauptstrasse 7, D-79104 Freiburg, Germany.
Int J Mol Med. 2003 Oct;12(4):597-601.
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.
CXC趋化因子1和8（CXCL1和CXCL8）是G蛋白偶联的CXC趋化因子受体2（CXCR2）的配体。趋化因子和CXCR2都是人黑素瘤细胞中一种有效的自分泌生长因子环的组成部分。目前，这两种趋化因子在正常人黑素细胞中的表达和生物学功能尚不清楚。在此我们描述，由碱性成纤维细胞生长因子（bFGF）、内皮素1（ET-1）和α-黑素细胞刺激素（α-MSH）组成的黑素细胞生长因子混合物可刺激CXCL1和CXCL8的释放，但不影响人黑素细胞中CXCR2的表达。细胞研究表明，CXCL1和CXCL8可增强生长因子（如bFGF、ET-1和α-MSH）混合物各种组合的增殖活性。此外，用抗CXCR2配体阻断抗体可降低bFGF、ET-1和α-MSH刺激后黑素细胞的增殖。本研究表明，CXCL1、CXCL8及其受体CXCR2是增殖的人黑素细胞自分泌机制的组成部分。
