Down regulation of CD4 expression in cultured microglia by immunosuppressants and lipopolysaccharide.
Microglia, brain macrophages, are thought to be the primary target of HIV-1 infection in the brain, because they exclusively express the CD4 antigen which is effectively used for viral entry. The expression of CD4 mRNA in cultured microglia could be detected by the reverse-PCR method. Using this and immunohistochemical staining, we found that the immunosuppressants cyclosporin A and FK506 decreased CD4 expression in cultured murine microglia without causing any significant decrease in cell viability. FK506 was more potent than cyclosporin A. Lipopolysaccharide also decreased CD4 mRNA expression in microglia. The effects of immunosuppressants and lipopolysaccharide seemed to be specific for microglia since these chemicals did not alter the CD4 expression in lymphocytes or peritoneal macrophages. These agents, if modified to pass through the blood-brain barrier, may prevent viral spread of HIV-1 infection in the central nervous system and the AIDS-dementia complex.
D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000166:cytology / Q000276:immunology*; D015704:CD4 Antigens / Q000096:biosynthesis* / Q000187:drug effects / Q000235:genetics; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D016572:Cyclosporine / Q000494:pharmacology; D015536:Down-Regulation; D015870:Gene Expression; D007150:Immunohistochemistry; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D051379:Mice; D008809:Mice, Inbred C3H; D010844:Picibanil / Q000494:pharmacology; D016133:Polymerase Chain Reaction / Q000379:methods; D012313:RNA / Q000235:genetics / Q000302:isolation & purification; D012333:RNA, Messenger / Q000378:metabolism; D016559:Tacrolimus / Q000494:pharmacology
D015704:CD4 Antigens; D007166:Immunosuppressive Agents; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D010844:Picibanil; D012313:RNA; D016572:Cyclosporine; D016559:Tacrolimus