Expression of chemokine genes in rat glial cells: the effect of myelin basic protein-reactive encephalitogenic T cells.
Chemokine gene expression and chemokine activity appear to be major components of the immunopathological processes of inflammation and autoimmunity. To initiate an investigation of the role of chemokines in the pathogenesis of autoimmune inflammatory demyelination, we examined the expression of mRNA transcripts encoding four prominent chemokines, IP-10, MIP-1 alpha, MCP-1, and RANTES, in encephalitogenic rat MBP-reactive T cells, astrocytes, and microglia. Astrocytes and microglia, whether as lines or as freshly isolated cells, did not constitutively express IP-10 and MCP-1 mRNA but could be induced with LPS to also produce MIP-1 alpha and RANTES. MBP-reactive T cells were induced with MBP to produce abundant levels of MIP-1 alpha, MCP-1, and RANTES mRNA in different temporal profiles but did not express IP-10 mRNA. In an MHC-II restricted fashion, the antigen-activated MBP-reactive T cells also induced glial cells to express all four chemokines, with the chemokine gene expression greatest following T-cell interactions with MHC-compatible glia. Treatment of glial cells with TNF-alpha and IFN-gamma induced only IP-10, indicating that the expression of chemokine genes other than IP-10 requires a combination of different cytokines or direct cell-cell contact between T cells and glia. Quantitative assays revealed that activated astrocytes, the dominant glia of the CNS, express higher levels of chemokine transcripts than transcripts of the major proinflammatory cytokines TNF-alpha and IFN-gamma. These results underscore the prominent but complex expression of chemokines by cellular component of inflammatory demyelinating lesions.
Sun
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Department of Neurology, University of Alabama at Birmingham 35294, USA.
Hu
X
X
Liu
X
X
Whitaker
J N
JN
Walker
W S
WS
D000818:Animals; D001253:Astrocytes / Q000378:metabolism; D002450:Cell Communication; D018925:Chemokines / Q000235:genetics*; D016207:Cytokines / Q000235:genetics / Q000494:pharmacology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000473:pathology*; D015870:Gene Expression; D005786:Gene Expression Regulation / Q000187:drug effects; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D008213:Lymphocyte Activation; D017628:Microglia / Q000378:metabolism; D004676:Myelin Basic Protein / Q000494:pharmacology*; D009457:Neuroglia / Q000502:physiology*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D013601:T-Lymphocytes / Q000187:drug effects* / Q000502:physiology*
D018925:Chemokines; D016207:Cytokines; D000949:Histocompatibility Antigens Class II; D004676:Myelin Basic Protein; D012333:RNA, Messenger