Induction of beta-family chemokines mRNA in human embryonic astrocytes by inflammatory cytokines and measles virus protein.
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.
Department of Clinical Neuroscience and Family Medicine, Karolinska Institute, Huddinge University Hospital, Stockholm, Sweden.
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BG
Xiao
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Mousa
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Kivisäkk
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A
Seiger
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Bakhiet
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Link
D001253:Astrocytes / Q000187:drug effects* / Q000378:metabolism*; D002478:Cells, Cultured; D019742:Chemokines, CC / Q000096:biosynthesis*; D016207:Cytokines / Q000494:pharmacology*; D003587:Cytomegalovirus / Q000276:immunology; D004305:Dose-Response Relationship, Drug; D004622:Embryo, Mammalian; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D007249:Inflammation / Q000378:metabolism; D007371:Interferon-gamma / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008459:Measles virus / Q000276:immunology; D012333:RNA, Messenger / Q000096:biosynthesis; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D014764:Viral Proteins / Q000494:pharmacology*
D019742:Chemokines, CC; D016207:Cytokines; D005904:Glial Fibrillary Acidic Protein; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D014764:Viral Proteins; D007371:Interferon-gamma