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Infection and Immunity, May 2001, p. 2847-2852, Vol. 69, No. 5
0019-9567/01/$04.00+0   DOI: 10.1128/IAI.69.5.2847-2852.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Gamma Interferon and Lipopolysaccharide Interact at the Level of Transcription To Induce Tumor Necrosis Factor Alpha Expression

Julia Y. Lee and Kathleen E. Sullivan*

Division of Immunologic and Infectious Diseases, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104

Received 11 October 2000/Returned for modification 12 December 2000/Accepted 31 January 2001

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.

* Corresponding author. Mailing address: Division of Immunologic and Infectious Diseases, Children's Hospital of Philadelphia, 34th St. and Civic Center Blvd., Philadelphia, PA 19104. Phone: (215) 590-4685. Fax: (215) 590-3044. E-mail: sullivak{at}mail.med.upenn.edu.

Infection and Immunity, May 2001, p. 2847-2852, Vol. 69, No. 5
0019-9567/01/$04.00+0   DOI: 10.1128/IAI.69.5.2847-2852.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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  • Garrett, S., Dietzmann-Maurer, K., Song, L., Sullivan, K. E. (2008). Polarization of Primary Human Monocytes by IFN-{gamma} Induces Chromatin Changes and Recruits RNA Pol II to the TNF-{alpha} Promoter. J. Immunol. 180: 5257-5266 [Abstract] [Full Text]  
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