Open AccessGamma Interferon and Lipopolysaccharide Interact at the Level of Transcription To Induce Tumor Necrosis Factor Alpha Expression
Author(s) -
Julia Y. Lee,
Kathleen E. Sullivan
Publication year - 2001
Publication title -
infection and immunity
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.508
H-Index - 220
eISSN - 1070-6313
pISSN - 0019-9567
DOI - 10.1128/iai.69.5.2847-2852.2001
Subject(s) - lipopolysaccharide , tumor necrosis factor alpha , biology , interferon gamma , cd14 , cytokine , downregulation and upregulation , microbiology and biotechnology , alpha (finance) , immunology , cancer research , immune system , medicine , biochemistry , gene , construct validity , nursing , patient satisfaction
Lipopolysaccharide (LPS) is a very potent inducer of tumor necrosis factor alpha (TNF-alpha) expression from monocytes and macrophages. Another inflammatory cytokine, gamma interferon (IFN-gamma), can potentiate the effects of LPS, but the mechanism is not thoroughly understood. Previous reports emphasized the ability of IFN-gamma to upregulate CD14 expression (the receptor for LPS), and nearly all studies have utilized sequential stimulation with IFN-gamma followed by LPS to exploit this phenomenon. This study demonstrates that IFN-gamma can upregulate the effect of LPS at the level of transcription. Human monoblastic Mono-Mac-6 cells produced up to threefold-greater levels of TNF-alpha when simultaneously stimulated with LPS and IFN-gamma compared to treatment with LPS alone. RNase protection studies showed a similar increase in RNA beginning as early as within 30 min. The synthesis of TNF-alpha mRNA in IFN-gamma- and LPS-treated Mono-Mac-6 cells was also temporally prolonged even though the message turnover rate was identical to that seen in LPS stimulated cells. The modulatory effect of IFN-gamma may be mediated by Jak2.