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 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-beta). TGF-beta, TNFalpha and IL-1beta, but not IFNgamma, induced MCP-1 mRNA and protein. TGF-beta, in cotreatment with TNFalpha caused an additive increase in MCP-1 mRNA, but not protein. In combination with IFNgamma, TGF-beta significantly increased MCP-1 mRNA and protein, as compared to either untreated, TGF-beta- or IFNgamma-treated astrocytes. However, TGF-gamma in cotreatment with IL-1beta decreased MCP-1 mRNA and protein, as compared to IL-1beta alone. Treatment of astrocytes with TGF-beta prior to TNFalpha, IFNgamma or IL-1beta 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.
Weiss
J M
JM
Department of Pathology, Albert Einstein College of Medicine, Bronx, NY 10461, USA. weiss@aecom.yu.edu
Berman
J W
JW
D001253:Astrocytes / Q000737:chemistry* / Q000502:physiology; D015152:Blotting, Northern; D001921:Brain / Q000166:cytology / Q000276:immunology; D018932:Chemokine CCL2 / Q000235:genetics / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D005333:Fetus / Q000166:cytology; D005434:Flow Cytometry; D015870:Gene Expression / Q000187:drug effects / Q000276:immunology; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D009000:Monocytes / Q000737:chemistry*; D012333:RNA, Messenger / Q000032:analysis; D016212:Transforming Growth Factor beta / Q000276:immunology* / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D018932:Chemokine CCL2; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma