Christine Power

MIG--differential gene expression in mouse brain endothelial cells.

Different diseases of the CNS are associated with blood–brain barrier (BBB) damage and mononuclear cell infiltration. In order to study genes that may play a role in endothelial cell regulation in inflammatory CNS diseases, we performed differential gene expression (DGE) analysis using a mouse brain endothelial cell line. We found that interferon-γ (IFNγ)-induced monokine (MIG), a chemokine that plays a role in T lymphocyte and monocyte chemoattraction, is highly expressed in the presence of inflammatory cytokines.We show that MIG, produced by brain endothelial cells in vitro, is biologically active in attracting T lymphocytes and that it is possible to interfere with this mechanism of action using anti-MIG antibodies. We suggest that blocking MIG may be beneficial in CNS inflammation. We detected constitutive expression of the MIG receptor, CXCR3, on the surface of the endothelial cells and therefore hypothesize that it plays a role in maintaining the cytokine gradient at the region of CNS inflammation.

Chemokines as drug targets

The question of how the migration of cells can be specifically controlled was first addressed at least 15 years ago with the identification of the neutrophil chemattractant, IL-8, and the monocyte attractants, MCP-1 and MIP-1α. The rapid expansion of this family of proteins, known as chemoattractant cytokines and re-named chemokines, showed that the idea of one chemokine being responsible for the recruitment of a single cell type was over simplistic in most cases.