Crucial role of interferon consensus sequence binding protein (ICSBP), but not of interferon regulatory factor (IRF) 1-induced nitric oxide for protection against murine listeriosis

1997 ◽  
Vol 56 (1-3) ◽  
pp. 358
Author(s):  
T Fehr
Keyword(s):  
Nitric Oxide ◽  
Crucial Role ◽  
Binding Protein ◽  
Consensus Sequence ◽  
Interferon Regulatory Factor ◽  
Regulatory Factor

scholarly journals Crucial Role of Interferon Consensus Sequence Binding Protein, but neither of Interferon Regulatory Factor 1 nor of Nitric Oxide Synthesis for Protection Against Murine Listeriosis

1997 ◽  
Vol 185 (5) ◽  
pp. 921-932 ◽  
Author(s):  
Thomas Fehr ◽  
Gabriele Schoedon ◽  
Bernhard Odermatt ◽  
Thomas Holtschke ◽  
Markus Schneemann ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Binding Protein ◽  
Consensus Sequence ◽  
Interferon Regulatory Factor ◽  
Regulatory Factor ◽  
Oxygen Intermediates ◽  
Ifn Γ ◽  
Effector Mechanisms

Listeria monocytogenes is widely used as a model to study immune responses against intracellular bacteria. It has been shown that neutrophils and macrophages play an important role to restrict bacterial replication in the early phase of primary infection in mice, and that the cytokines interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α) are essential for protection. However, the involved signaling pathways and effector mechanisms are still poorly understood. This study investigated mouse strains deficient for the IFN-dependent transcription factors interferon consensus sequence binding protein (ICSBP), interferon regulatory factor (IRF)1 or 2 for their capacity to eliminate Listeria in vivo and in vitro and for production of inducible reactive nitrogen intermediates (RNI) or reactive oxygen intermediates (ROI) in macrophages. ICSBP−/− and to a lesser degree also IRF2−/− mice were highly susceptible to Listeria infection. This correlated with impaired elimination of Listeria from infected peritoneal macrophage (PEM) cultures stimulated with IFN-γ in vitro; in addition these cultures showed reduced and delayed oxidative burst upon IFN-γ stimulation, whereas nitric oxide production was normal. In contrast, mice deficient for IRF1 were not able to produce nitric oxide, but they efficiently controlled Listeria in vivo and in vitro. These results indicate that (a) the ICSBP/IRF2 complex is essential for IFN-γ–mediated protection against Listeria and that (b) ROI together with additional still unknown effector mechanisms may be responsible for the anti-Listeria activity of macrophages, whereas IRF1-induced RNI are not limiting.

scholarly journals Interferon consensus sequence-binding protein, a member of the interferon regulatory factor family, suppresses interferon-induced gene transcription.

1993 ◽  
Vol 13 (1) ◽  
pp. 588-599 ◽  
Author(s):  
N Nelson ◽  
M S Marks ◽  
P H Driggers ◽  
K Ozato
Keyword(s):  
Major Histocompatibility Complex ◽  
Retinoic Acid ◽  
Major Histocompatibility Complex Class ◽  
Binding Protein ◽  
Consensus Sequence ◽  
Interferon Regulatory Factor ◽  
Chloramphenicol Acetyltransferase ◽  
Complex Class ◽  
Regulatory Factor ◽  
Histocompatibility Complex

We previously isolated a cDNA clone encoding interferon consensus sequence-binding protein (ICSBP), a member of the interferon regulatory factor (IRF) family, that binds to the interferon (IFN)-stimulated response element (ISRE) of many IFN-regulated genes. In this investigation, we studied the functional role of ICSBP by transient cotransfection of ICSBP cDNA with IFN-responsive reporter genes into the human embryonal carcinoma cell line N-Tera2. These cells were shown not to express ICSBP or IRF-2, thus allowing functional analysis of transfected cDNAs. Cotransfection of ICSBP into cells treated with retinoic acid or any of the IFNs (alpha, beta, or gamma) repressed expression of a chloramphenicol acetyltransferase reporter driven by the major histocompatibility complex class I gene promoter. Similarly, ICSBP repressed expression of chloramphenicol acetyltransferase reporters driven by the ISREs of the 2'-5' oligoadenylate synthetase, guanylate-binding protein, and ISG-15 genes in IFN-treated cells. The repression was dependent on the presence of the ISRE in the reporter. Deletion analysis showed that the putative N-terminal DNA binding domain of ICSBP by itself is capable of mediating the repression. Using the same cotransfection conditions as for ICSBP, a similar repression of these reporters was observed with IRF-2. Finally, ICSBP repressed the IRF-1-mediated induction of major histocompatibility complex class I and IFN-beta reporters in the absence of IFN or retinoic acid. Taken together, these results suggest that ICSBP is a negative regulatory factor capable of repressing transcription of target genes induced by IFN, retinoic acid, or IRF-1.

Interferon consensus sequence-binding protein, a member of the interferon regulatory factor family, suppresses interferon-induced gene transcription

1993 ◽  
Vol 13 (1) ◽  
pp. 588-599
Author(s):  
N Nelson ◽  
M S Marks ◽  
P H Driggers ◽  
K Ozato
Keyword(s):  
Major Histocompatibility Complex ◽  
Retinoic Acid ◽  
Major Histocompatibility Complex Class ◽  
Binding Protein ◽  
Consensus Sequence ◽  
Interferon Regulatory Factor ◽  
Chloramphenicol Acetyltransferase ◽  
Complex Class ◽  
Regulatory Factor ◽  
Histocompatibility Complex

We previously isolated a cDNA clone encoding interferon consensus sequence-binding protein (ICSBP), a member of the interferon regulatory factor (IRF) family, that binds to the interferon (IFN)-stimulated response element (ISRE) of many IFN-regulated genes. In this investigation, we studied the functional role of ICSBP by transient cotransfection of ICSBP cDNA with IFN-responsive reporter genes into the human embryonal carcinoma cell line N-Tera2. These cells were shown not to express ICSBP or IRF-2, thus allowing functional analysis of transfected cDNAs. Cotransfection of ICSBP into cells treated with retinoic acid or any of the IFNs (alpha, beta, or gamma) repressed expression of a chloramphenicol acetyltransferase reporter driven by the major histocompatibility complex class I gene promoter. Similarly, ICSBP repressed expression of chloramphenicol acetyltransferase reporters driven by the ISREs of the 2'-5' oligoadenylate synthetase, guanylate-binding protein, and ISG-15 genes in IFN-treated cells. The repression was dependent on the presence of the ISRE in the reporter. Deletion analysis showed that the putative N-terminal DNA binding domain of ICSBP by itself is capable of mediating the repression. Using the same cotransfection conditions as for ICSBP, a similar repression of these reporters was observed with IRF-2. Finally, ICSBP repressed the IRF-1-mediated induction of major histocompatibility complex class I and IFN-beta reporters in the absence of IFN or retinoic acid. Taken together, these results suggest that ICSBP is a negative regulatory factor capable of repressing transcription of target genes induced by IFN, retinoic acid, or IRF-1.

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