REGULATION OF BETA -CHEMOKINE MRNA EXPRESSION IN ADULT RAT ASTROCYTES BY LIPOPOLYSACCHARIDE, PROINFLAMMATORY AND IMMUNOREGULATORY CYTOKINES

Astrocytes constitute a part of the blood–brain barrier. Chemokine expression by astrocytes may contribute to leucocyte infiltration within the central nervous system (CNS) during inflammation. To investigate factor(s) regulating chemokine expression by astrocytes, we studied the induction of β-chemokine mRNA expression in adult rat astrocytes. Astrocyte-derived monocyte chemoattractant protein-1 (MCP-1), RANTES, macrophage inflammatory protein (MIP)-1α and MIP-1β mRNA were induced by interferon-γ (IFN-γ). Tumour necrosis factor-α (TNF-α) induced MCP-1, RANTES and MIP-1β mRNA expression, and lipopolysaccharide (LPS) induced MCP-1, MIP-1α and MIP-1β mRNA expression in astrocytes. LPS-induced MCP-1, MIP-1α and MIP-1β mRNA expression by astrocytes was antagonized by transforming growth factor (TGF)-β1 and interleukin (IL)-10. TGF-β1 and IL-10 also down-regulated MCP-1 and RANTES mRNA expression induced by TNF-α. IL-10, but not TGF-β1, inhibited MIP-1β mRNA expression induced by TNF-α. The results of this in vitro study suggest that β-chemokine mRNA expression by adult rat astrocytes can be induced by LPS or proinflammatory cytokines, while regulatory cytokines, such as TGF-β1 and IL-10, down-regulate astrocyte-derived β-family chemokine mRNA expression induced by LPS, IFN-γ and TNF-α. Further study of CNS chemokines will enhance our understanding of leucocyte recruitment to the CNS and suggest therapeutic strategies for neurological disorders.