Cytokine regulation of MCP-1 expression in brain and retinal microvascular endothelial cells.
Chemokines have a pivotal role in the selective mediation and amplification of inflammation. The CNS vascular endothelial cells, which form part of the blood-brain barrier (BBB) and blood-retinal barrier (BRB), are ideally situated to present chemokines to circulating lymphocytes leading to their recruitment. Monocyte-chemoattractant protein-1 (MCP-1), also known as CCL2, a potent chemoattractant of T cells and monocytes, has been implicated in inflammatory and angio-proliferative brain and retinal disease. In this study, MCP-1 expression by CNS endothelial cells was investigated in vitro. Rat brain (GP8/3.9) and retinal (JG2/1) vascular endothelial cell lines expressed MCP-1 constitutively in vitro as assessed by immunocytochemistry and enzyme linked immunosorbant assay (ELISA). Upregulation of secreted MCP-1 was observed following activation with the pro-inflammatory cytokines TNF-alpha, IL-1 beta and IFN-gamma, and was reduced following dexamethasone treatment. Functional chemotactic activity of brain and retinal endothelial cell supernatants was demonstrated in an in vitro chemotaxis assay, which was inhibited by anti-MCP-1 antibodies. These findings suggest that endothelial cell-derived MCP-1 plays a key role in leukocyte recruitment across the blood-brain and blood-retinal barriers in vivo.
D000818:Animals; D001921:Brain / Q000098:blood supply* / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D002460:Cell Line; D002474:Cell-Free System / Q000276:immunology; D018932:Chemokine CCL2 / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000378:metabolism; D002634:Chemotaxis, Leukocyte / Q000276:immunology; D016207:Cytokines / Q000494:pharmacology / Q000502:physiology*; D003907:Dexamethasone / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D005260:Female; D007166:Immunosuppressive Agents / Q000494:pharmacology; D007371:Interferon-gamma / Q000494:pharmacology; D007375:Interleukin-1 / Q000494:pharmacology; D007424:Intracellular Fluid / Q000276:immunology / Q000378:metabolism; D008833:Microcirculation / Q000166:cytology / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D051381:Rats; D011917:Rats, Inbred Lew; D012171:Retinal Vessels / Q000166:cytology / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D018932:Chemokine CCL2; D016207:Cytokines; D007166:Immunosuppressive Agents; D007375:Interleukin-1; D014409:Tumor Necrosis Factor-alpha; D003907:Dexamethasone; D007371:Interferon-gamma