Cytokine regulation of MCP-1 expression in brain and retinal microvascular endothelial cells

J Neuroimmunol. 2003 Sep;142(1-2):1-9. doi: 10.1016/s0165-5728(03)00251-0.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain / blood supply*
  • Brain / cytology
  • Brain / immunology*
  • Brain / metabolism
  • Cell Line
  • Cell-Free System / immunology
  • Chemokine CCL2 / antagonists & inhibitors
  • Chemokine CCL2 / biosynthesis*
  • Chemokine CCL2 / metabolism
  • Chemotaxis, Leukocyte / immunology
  • Cytokines / pharmacology
  • Cytokines / physiology*
  • Dexamethasone / pharmacology
  • Endothelium, Vascular / cytology
  • Endothelium, Vascular / drug effects
  • Endothelium, Vascular / immunology*
  • Endothelium, Vascular / metabolism
  • Female
  • Immunosuppressive Agents / pharmacology
  • Interferon-gamma / pharmacology
  • Interleukin-1 / pharmacology
  • Intracellular Fluid / immunology
  • Intracellular Fluid / metabolism
  • Microcirculation / cytology
  • Microcirculation / drug effects
  • Microcirculation / immunology
  • Microcirculation / metabolism
  • Rats
  • Rats, Inbred Lew
  • Retinal Vessels / cytology
  • Retinal Vessels / drug effects
  • Retinal Vessels / immunology*
  • Retinal Vessels / metabolism
  • Tumor Necrosis Factor-alpha / pharmacology

Substances

  • Chemokine CCL2
  • Cytokines
  • Immunosuppressive Agents
  • Interleukin-1
  • Tumor Necrosis Factor-alpha
  • Dexamethasone
  • Interferon-gamma