Synergism between interferon-gamma and cytokines or lipopolysaccharide in the activation of the HIV-LTR in macrophages.
Macrophages (møs) obtained from transgenic mice carrying the HIV long terminal repeat-chloramphenicol acetyl transferase (LTR-CAT) sequence were used to study the influence of various biologic response modifiers (BRMs) on the activation of LTR-directed CAT expression. It was found that LPS or IL-6 alone induced moderate levels of CAT expression, whereas IFN-gamma or TNF-alpha had no significant effect. Co-exposure of møs to IFN-gamma and either LPS, IL-6, or TNF-alpha led to significant synergistic increases in CAT levels. Levels were also synergistically augmented when møs were exposed first to IFN-gamma (priming), washed, and then exposed to either LPS, IL-6, or TNF-alpha. Although IL-6 was synergistic with subsequently added IFN-gamma, the reverse sequence of addition was more effective. LPS and TNF-alpha were inactive when added before IFN-gamma. Initial priming signals were rapid as exposure for 3 h to IFN-gamma was sufficient to prepare the cells for subsequent activation by other BRMs. These results suggest that the duration of latency and progression of HIV infections may be greatly influenced by events such as intercurrent infections that cause IFN-gamma production, thereby priming møs to respond to other cytokines that have been reported to be constitutively elevated during the course of infection with HIV (e.g., IL-6 and/or TNF-alpha).
Warfel
A H
AH
Department of Dermatology, New York University School of Medicine, New York.
Thorbecke
G J
GJ
Belsito
D V
DV
D000818:Animals; D016207:Cytokines / Q000008:administration & dosage*; D005260:Female; D015967:Gene Expression Regulation, Viral / Q000187:drug effects*; D016325:HIV Long Terminal Repeat / Q000235:genetics*; D015497:HIV-1 / Q000235:genetics*; D007371:Interferon-gamma / Q000008:administration & dosage*; D008070:Lipopolysaccharides / Q000008:administration & dosage*; D017737:Macrophages, Peritoneal / Q000382:microbiology*; D008297:Male; D051379:Mice; D011994:Recombinant Proteins; D014158:Transcription, Genetic / Q000187:drug effects
D016207:Cytokines; D008070:Lipopolysaccharides; D011994:Recombinant Proteins; D007371:Interferon-gamma