Induction of beta-family chemokines mRNA in human embryonic astrocytes by inflammatory cytokines and measles virus protein.

Abstract

The cellular infiltration found during CNS inflammation consists of monocytes and activated T cells, suggesting the presence of cell-specific chemotactic signals during inflammatory responses. Astrocyte chemokine expression might contribute to site-specific leukocyte infiltration within the CNS. To investigate the factors that regulate astrocyte chemokine expression, we examined the ability of human fetal astrocytes to induce beta-family chemokine mRNA. Astrocyte-derived monocyte chemoattractant protein-1 (MCP-1), RANTES, macrophage inflammatory protein-1alpha (MIP-1alpha), and MIP-1beta mRNA were easily induced by lipopolysaccharide and/or the proinflammatory cytokines (IFN-gamma and/or TNF-alpha), respectively. Addition of both IFN-gamma and TNF-alpha together did not lead to an additive effect but resulted in the inhibition of MCP-1 and MIP-1beta mRNA expression, indicating that interaction between chemokines and cytokines may play a key role in regulating the local immune response of resident and infiltrating cells at the site of lesion. Interestingly, ultraviolet light-inactivated measles virus, but not cytomegalovirus, strongly induced expression of MCP-1, RANTES, MIP-1alpha, and MIP-1beta mRNA in human embryonic astrocytes, especially MCP-1 and MIP-1beta. An association occurs between the beta-family chemokine expression in astrocytes and inflammatory factors/virus, suggesting a possible role for beta-family chemokines in the pathogenesis of CNS inflammatory disease.