The pathophysiology of central nervous system (CNS) inflammatory disease is dependent, in part, on leukocyte recruitment across the blood-brain barrier. 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 activated T cells. We examined the regulation of MCP-1 expression in human fetal astrocytes following cytokine treatment in the presence and absence of transforming growth factor beta (TGF-β). TGF-β, TNFα and IL-1β, but not IFNγ, induced MCP-1 mRNA and protein, TGF-β, in cotreatment with TNFα caused an additive increase in MCP-1 mRNA, but not protein. In combination with IFNγ, TGF-β significantly increased MCP-1 mRNA and protein, as compared to either untreated, TGF-β or IFNγ-treated astrocytes. However, TGF-β in cotreatment with IL-1β decreased MCP-1 mRNA and protein, as compared to IL-1β alone. Treatment of astrocytes with TGF- β prior to TNFα, IFNγ or IL-1β treatment significantly 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.
- Monocyte chemoattractant protein-1
- Transforming growth factor beta
ASJC Scopus subject areas
- Immunology and Allergy
- Clinical Neurology