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Synergism between interferon‐γ and cytokines or lipopolysaccharide in the activation of the HIV‐LTR in macrophages
Author(s) -
Warfel Alwin H.,
Thorbecke G. Jeanette,
Belsito Donald V.
Publication year - 1995
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1002/jlb.57.3.469
Subject(s) - priming (agriculture) , lipopolysaccharide , biology , tumor necrosis factor alpha , interferon gamma , immunology , gamma interferon , cytokine , microbiology and biotechnology , botany , germination
Macrophages (mfs) 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‐γ or TNF‐α had no significant effect. Co‐exposure of m φ s to IFN‐γ and either LPS, IL‐6, or TNF‐α led to significant synergistic increases in CAT levels. Levels were also synergistically augmented when m φ s were exposed first to IFN‐γ (priming), washed, and then exposed to either LPS, IL‐6, or TNF‐α. Although IL‐6 was synergistic with subsequently added IFN‐γ, the reverse sequence of addition was more effective. LPS and TNF‐α were inactive when added before IFN‐γ. Initial priming signals were rapid as exposure for 3 h to IFN‐γ 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‐γ production, thereby priming mfs 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‐α). J. Leukoc. Biol . 57: 469–476; 1995.