Different mechanisms for activation of gene transcription by interferons α and γ

Faltynek, Connie R.; McCandless, Sarah; Chebath, Judith; Baglioni, Corrado

doi:10.1016/0042-6822(85)90315-0

Cited by 40 publications

(38 citation statements)

References 11 publications

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“…1B). The kinetics of induction of this mRNA, mRNA 561, in HeLa monolayer cells were similar to what has been reported for other cell lines (1,4). A high level of this mRNA accumulated after 6 h of IFN-aA treatment; the level then decreased rapidly as treatment was continued for 12 or 24 h (Fig.…”

Section: Resultssupporting

confidence: 64%

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Regulation of synthesis and turnover of an interferon-inducible mRNA.

Kusari¹,

Sen²

1986

Mol. Cell. Biol.

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Regulation of synthesis and turnover of an interferon (IFN)-inducible mRNA, mRNA 561, in HeLa monolayer cells was studied. Cytoplasmic levels of this mRNA were estimated by hybridization analyses with a cDNA clone that we have isolated as a probe. IFN-aoA induced a high level of this mRNA in a transient fashion, whereas no induction was observed in response to IFN--y. Surprisingly little mRNA 561 was induced in cells treated simultaneously with IFN-aA and an inhibitor of protein synthesis, suggesting that in addition to IFN-atA, an interferon-inducible protein was needed for induction of this mRNA. Apparently this putative protein could be induced by IFN-y as well. Thus, although little mRNA 561 was synthesized in cells treated either with IFN--y alone or with IFN-aA and cycloheximide, a large quantity of this mRNA was induced in cells which had been pretreated with IFN-y and then treated with IFN-aA and cycloheximide. Once mRNA 561 was induced by IFN-aA, it turned over rapidly. This rapid turnover could be blocked by actinomycin D or cycloheximide indicating that another IFN-inducible protein may mediate this process.

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Section: Resultssupporting

confidence: 64%

“…Total cytoplasmic RNA was analyzed by dot hybridization as described by White and Bancroft (21). All RNA samples were analyzed at four serial twofold dilutions containing 16,8,4, and 2 ,ug of total RNA. The autoradiograms were scanned with a densitometer equipped with an integrator.…”

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confidence: 99%

Regulation of synthesis and turnover of an interferon-inducible mRNA.

Kusari¹,

Sen²

1986

Mol. Cell. Biol.

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“…The same remarks can be made when the induction of the endogeneous 2-5A synthetase activity [11,12,23] or mRNA is measured [5,6,13,14], meaning that the difference comes mainly from the transcriptional effects of IFNs. The delay in obtaining the maximal response to IFNy and the effect of cycloheximide suggest that the synthesis of a new protein is needed to obtain the transcriptional effect of IFNy, and that the two IFNs stimulate the IRS by different mechanisms.…”

Section: Discussionmentioning

confidence: 97%

“…The two types of IFNs differ, however, notably in their structure, their cell surface receptors, and their biological activities [2,3]. It is therefore logical that the characteristics of induction of the cloned 2-SA synthetase mRNAs [4] by the two IFNs are not similar [5,6]. The mRNAs are induced much less by IFNy than by type I IFNs [5,6].…”

Section: Introductionmentioning

confidence: 99%

“…It is therefore logical that the characteristics of induction of the cloned 2-SA synthetase mRNAs [4] by the two IFNs are not similar [5,6]. The mRNAs are induced much less by IFNy than by type I IFNs [5,6]. In HeLa cells, their induction by IFNy can be abolished by the protein synthesis inhibitor cycloheximide, while their induction by IFNcv is, in general, not sensitive to cycloheximide [5] and considered as a direct effect on transcription (71.…”

Section: Introductionmentioning

confidence: 99%

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Synergism of type I and type II Interferons in stimulating the activity of the same DNA enhancer

Vaiman¹,

Pietrokovsky²,

Cohen³

et al. 1990

FEBS Letters

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Type I and type II interferons (IFNs) can act synergistically to activate the transcription of the 2-SA synthetase gene. We used in vivo functional assays of sequences from the gene promoter region to determine which DNA segment mediates the gene induction by IFNy and the synergistic effect. We found that the type I IFN-inducible enhancer (or IRS) of the 2-5A synthetase gene also confers inducibility by type II IFN to a reporter CAT gene, though the time course and dose response of the induction by the two IFNs are quite different. A clear synergism of the two IFNs in stimulating the IRS is observed at low doses of the two IFNs.2-5A Synthetase; Type I interferon-inducible enhancer synergistic activation type I interferon; Type II interferon

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Interferon‐γ activates multiple pathways to regulate the expression of the genes for major histocompatibility class II I‐Aβ, tumor necrosis factor and complement component C3 in mouse macrophages

1989

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The purpose of this study was to obtain additional information on the mechanism by which interferon-gamma (IFN-gamma) is able to regulate gene expression in macrophages. The expression of the genes for class II histocompatibility I-A beta, tumor necrosis factor (TNF) and complement component C3 was assayed after treating bone marrow macrophages with IFN-gamma. Each gene displayed a characteristic pattern of regulation. First, the increase in the level of RNA for each gene followed different kinetics. The level of TNF RNA increased within 15 min after IFN-gamma treatment and reached a plateau after 4 h. In contrast, there was a lag of about 4 h before the level of I-A beta RNA began to rise and a plateau was not reached until 48 h after the IFN-gamma treatment began. C3 gene expression followed an intermediate time course between that for TNF and I-A beta. Second, the expression of I-A beta was inhibited when cells were treated with both IFN-gamma and cycloheximide, while the expression of TNF and C3 was not. Interestingly, the sensitivity to cycloheximide only lasted 30 min following the addition of IFN-gamma, after which cycloheximide had no effect on the expression of I-A beta. Third, lipopolysaccharide abolished the IFN-gamma-induced expression of I-A beta, but enhanced the expression of TNF. Based on these observations, we conclude that IFN-gamma must activate multiple pathways to regulate gene expression in macrophages.

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Different mechanisms for activation of gene transcription by interferons α and γ

Cited by 40 publications

References 11 publications

Regulation of synthesis and turnover of an interferon-inducible mRNA.

Regulation of synthesis and turnover of an interferon-inducible mRNA.

Synergism of type I and type II Interferons in stimulating the activity of the same DNA enhancer

Interferon‐γ activates multiple pathways to regulate the expression of the genes for major histocompatibility class II I‐Aβ, tumor necrosis factor and complement component C3 in mouse macrophages

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