Neurotrophins and the anti-inflammatory agents interleukin-4 (IL-4), IL-10, IL-11 and transforming growth factor-beta1 (TGF-beta1) down-regulate T cell costimulatory molecules B7 and CD40 on cultured rat microglia.
Microglia are essential for T cell activation in the CNS. Since T cell activation requires costimulation by B7 and/or CD40, we examined the regulation by cytokines of B7-1, B7-2 and CD40 mRNA expression in cultured rat microglia in serum-free medium. All three ligands are expressed constitutively, but are profoundly up-regulated by granulocyte-macrophage colony-stimulating factor (GM-CSF). By contrast, interferon-gamma raises only B7-2 and CD40 mRNA, and the B7-2 increase is inhibited by IL-10. IL-4, transforming growth factor-beta1, and nerve growth factor (NGF) repress GM-CSF-induced B7-2 and CD40, but not B7-1. NGF also down-regulates its own high-affinity trkA receptor. IL-11, unrecognized for its effect on antigen presentation, represses GM-CSF-induced B7-2.
Wei
R
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Department of Biological Sciences, Rutgers University, Newark, NJ 07102-1811, USA.
Jonakait
G M
GM
D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism; D000970:Antineoplastic Agents / Q000494:pharmacology; D018122:B7-1 Antigen / Q000235:genetics / Q000378:metabolism*; D051940:B7-2 Antigen; D019013:CD40 Antigens / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D016895:Culture Media, Serum-Free / Q000494:pharmacology; D015342:DNA Probes; D015536:Down-Regulation / Q000187:drug effects / Q000276:immunology; D005786:Gene Expression Regulation / Q000187:drug effects / Q000276:immunology; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D007371:Interferon-gamma / Q000494:pharmacology; D016753:Interleukin-10 / Q000494:pharmacology; D017370:Interleukin-11 / Q000494:pharmacology; D015847:Interleukin-4 / Q000494:pharmacology; D007378:Interleukins / Q000494:pharmacology*; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism; D017628:Microglia / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D009414:Nerve Growth Factors / Q000494:pharmacology*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016212:Transforming Growth Factor beta / Q000494:pharmacology*; D015854:Up-Regulation / Q000187:drug effects / Q000276:immunology
D015703:Antigens, CD; D000970:Antineoplastic Agents; D018122:B7-1 Antigen; D051940:B7-2 Antigen; D019013:CD40 Antigens; C497966:Cd86 protein, rat; D016895:Culture Media, Serum-Free; D015342:DNA Probes; D017370:Interleukin-11; D007378:Interleukins; D008562:Membrane Glycoproteins; D009414:Nerve Growth Factors; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D016753:Interleukin-10; D015847:Interleukin-4; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor