Astrocyte expression of monocyte chemoattractant protein-1 is differentially regulated by transforming growth factor beta

The pathophysiology of central nervous system (CNS) inflammatory disease is dependent, in part, on leukocyte recruitment across the blood-brain barrie r. The expression of cytokines and chemokines by astrocytes may contribute to this process. Astrocytes express monocyte chemoattractant protein-1 (MCP -1), an activator of monocytes and a chemoattractant for monocytes and acti vated T cells, We examined the regulation of MCP-1 expression inhuman fetal astrocytes following cytokine treatment in the presence and absence of tra nsforming growth factor beta(TGF-beta). TGF-beta. TNF alpha and IL-1 beta, but not IFN gamma, induced MCP-1 mRNA and protein. TGF-beta, in cotreatment with TNF alpha caused an additive increase in MCP-1 mRNA, but not protein. In combination with IFN gamma, TGF-beta significantly increased MCP-1 mRNA and protein, as compared to either untreated, TGF-beta- or IFN gamma-treat ed astrocytes. However, TGF-beta in cotreatment with IL-1 beta decreased MC P-1 mRNA and protein, as compared to IL-1 beta alone. Treatment of astrocyt es with TGF-beta prior to TNF alpha, IFN gamma or IL-1 beta treatment signi ficantly increased MCP-1 expression. The kinetics of cytokine expression in the CNS may differentially regulate astrocyte-derived MCP-1 expression and subsequent recruitment and activation of leukocytes. (C) 1998 Elsevier Sci ence B.V. All rights reserved.