Abstract:
:Previous studies from our laboratory have shown that prolonged exposure of mouse macrophages to IFN-beta interferes with their subsequent ability to become activated for tumor cell killing. Data reported here show that such inhibition is due to reduced production of NO, resulting from decreased transcription of the gene that encodes inducible NO synthase (iNOS; EC 1.14.13.39). The molecular basis for such suppression was shown to be, at least in part, decreased nuclear accumulation of tyrosine-phosphorylated Stat1alpha (pStat1alpha), and a consequent change in the nuclear ratio of pStat1alpha to non-transactivating pStat1beta. Reduced phosphorylation was observed despite the fact that time-course studies revealed greater than normal quantities of both Stat1alpha and Stat1beta proteins in macrophages that had been pre-exposed to IFN-beta. The decrease in nuclear pStat1alpha was demonstrated to involve an increase in the rate of turnover of phosphorylated protein. The homodimeric form of pStat1alpha is essential for the expression of both the iNOS and IFN-regulatory factor-1 genes (the product of the latter is necessary for full expression of the iNOS gene). These results have broad implications, because they suggest that limiting the availability of homodimeric pStat1alpha is a means by which down-regulation of genes containing promoter-linked IFN-gamma-activated sites might be achieved.
journal_name
Eur J Immunoljournal_title
European journal of immunologyauthors
Gao JJ,Filla MB,Lorsbach RB,Pace JL,Crespo A,Russell SW,Murphy WJdoi
10.1002/1521-4141(200006)30:6<1551::AID-IMMU1551>3keywords:
subject
Has Abstractpub_date
2000-06-01 00:00:00pages
1551-61issue
6eissn
0014-2980issn
1521-4141pii
10.1002/1521-4141(200006)30:6<1551::AID-IMMU1551>3journal_volume
30pub_type
杂志文章abstract::T cell activation and cytokine secretion are important mediators of inflammation in allergic asthma. The costimulatory pathway CD28/CD80/CD86 has been shown to play an important role in T cell activation in allergic asthma, but less is known about the effect of other costimulatory molecules in allergy. The costimulato...
journal_title:European journal of immunology
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abstract::Cervical thymus mimics the thoracic thymus in supporting T-cell development and exists in a subset of mice and humans. Importantly, it remains unknown whether the cervical thymus can generate T cells that are self-tolerant in the complete absence of signals from the thoracic thymus. Using a fetal liver reconstitution ...
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journal_title:European journal of immunology
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journal_title:European journal of immunology
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journal_title:European journal of immunology
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更新日期:1991-01-01 00:00:00
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journal_title:European journal of immunology
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journal_title:European journal of immunology
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journal_title:European journal of immunology
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journal_title:European journal of immunology
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journal_title:European journal of immunology
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