Expression of complement inhibitor protein CD59 in human neuronal and glial cell lines treated with HIV-1 gp41 peptides.
In attempts to elucidate the pathogenic mechanisms involved in neurodegeneration in AIDS patients with cognitive deficits, the possible effect of HIV-1 transmembrane envelope protein gp41 on expression of the membrane inhibitor of complement mediated cytolysis (CD59) was assessed in human neuronal (SK-N-SH) and astroglial (T98G) cell lines. Western blotting analyses demonstrated that an immunodominant (ID, aa 598-613) gp41 peptide as well as the recombinant gp41 protein encompassing this domain markedly reduced CD59 level in a dose dependent manner whereas p24 and control peptide had little effect. RT-PCR showed that ID peptide also elicited a reduction in the expressed CD59 mRNA level. This gp41 peptide apparently down-regulated phorbol 12,13-dibutyrate induced elevation of CD59 at the protein and mRNA levels in a manner similar to that conferred by protein kinase C inhibitor, H-7 or staurosporine in SK-N-SH. Interestingly, proinflammatory cytokines such as IL-1beta or IFN-gamma as well as LPS greatly decreased CD59 in SK-N-SH and to a lesser extent in T98G whereas TNF-alpha did not significantly alter it. In contrast, antioxidants and anti-inflammatory agents enhanced CD59 expression reversing gp41 peptide mediated inhibitory effect in SK-N-SH. Our data suggest that high level of gp41 or its metabolites as well as impaired protein kinase response, chronic inflammation or antioxidant depletion within HIV-1 infected brains may be associated with a diminished expression of CD59 which would render neuronal cells to susceptible to indirect bystander lysis in the presence of autologous complement.
Chong
Y H
YH
Department of Microbiology, College of Medicine, Medical Research Center, Ewha Womans University, Seoul, Korea.
Lee
M J
MJ
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / Q000494:pharmacology; D018957:CD59 Antigens / Q000096:biosynthesis* / Q000235:genetics; D002273:Carcinogens / Q000494:pharmacology; D002460:Cell Line; D003169:Complement Inactivator Proteins / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015700:HIV Envelope Protein gp41 / Q000276:immunology / Q000494:pharmacology*; D006801:Humans; D016056:Immunodominant Epitopes / Q000276:immunology / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D009457:Neuroglia / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D010446:Peptide Fragments / Q000276:immunology / Q000494:pharmacology; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000187:drug effects; D012333:RNA, Messenger / Q000378:metabolism; D019311:Staurosporine / Q000494:pharmacology
D018957:CD59 Antigens; D002273:Carcinogens; D003169:Complement Inactivator Proteins; D004791:Enzyme Inhibitors; D015700:HIV Envelope Protein gp41; D016056:Immunodominant Epitopes; D008070:Lipopolysaccharides; D010446:Peptide Fragments; D012333:RNA, Messenger; D015240:Phorbol 12,13-Dibutyrate; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D011493:Protein Kinase C; D019311:Staurosporine