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.
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-
) expression from monocytes and macrophages. Another inflammatory cytokine, gamma interferon (IFN-
), can
potentiate the effects of LPS, but the mechanism is not thoroughly
understood. Previous reports emphasized the ability of IFN-
to
upregulate CD14 expression (the receptor for LPS), and nearly all
studies have utilized sequential stimulation with IFN-
followed by
LPS to exploit this phenomenon. This study demonstrates that IFN-
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-
when simultaneously stimulated with LPS and IFN-
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-
mRNA in IFN-
- 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-
may be mediated by Jak2.
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