THE CHEMOKINE REPERTOIRE OF HUMAN DERMAL MICROVASCULAR ENDOTHELIAL-CELLS AND ITS REGULATION BY INFLAMMATORY CYTOKINES

Activation of endothelium is a critical event during the initiation of inflammatory processes and is associated with the induction of cell a dhesion molecules and cytokines, The latter include chemotactically ac tive cytokines (chemokines) that promote leukocyte diapedesis from the circulation to sites of evolving inflammation, In this study we evalu ated the chemokine repertoire of human endothelial cells derived from the skin (HDMECs) and regulation of these chemokines by cytokines, HDM ECs and an immortalized human dermal microvascular endothelial cell li ne, HMEC-1, were investigated for the expression of C-X-C and C-C chem okines at mRNA and protein levels, Upon stimulation with interleukin-1 beta (IL-1 beta) and tumor necrosis factor-alpha (TNF-alpha), both HD MECs and HMEC-1 expressed high levels of ILS, GRO, and monocyte chemoa ttractant protein-1 (MCP-I), RANTES was only weakly induced; however, concomitant treatment with TNF-alpha and interferon-gamma (IFN-gamma) led to upregulation of RANTES, indicating a synergy between these two cytokines, The C-X-C chemokine IFN-inducible protein-ill was upregulat ed by IFN-gamma but not by other cytokines studied, Macrophage inflamm atory protein-1 alpha and beta, I-309, and ENA-78 could not be induced . The chemokine repertoires of HDMECs and HMEC-1 were compared to thos e of hunan umbilical vein endothelium and found to be rather similar w ith the important exception that IFN-gamma and IL-4 up-regulated MCP-1 only in macrovascular endothelium. Our data indicate that HDMECs cont ribute to the dermal cytokine network by selective production of MCP-1 , IL-8, GRO, RANTES, and IP-10, which may critically influence the sit e-specific recruitment of leukocyte subsets.