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The transcription factor interferon regulatory factor 1 is expressed after cerebral ischemia and contributes to ischemic brain injury.

Iadecola C, Salkowski CA, Zhang F, Aber T, Nagayama M, Vogel SN, Ross ME - J. Exp. Med. (1999)

Bottom Line: The transcription factor interferon regulatory factor 1 (IRF-1) is involved in the molecular mechanisms of inflammation and apoptosis, processes that contribute to ischemic brain injury.The reduction in infarct volume was paralleled by a substantial attenuation in neurological deficits.Thus, IRF-1 is the first nuclear transacting factor demonstrated to contribute directly to cerebral ischemic damage and may be a novel therapeutic target in ischemic stroke.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurology, University of Minnesota, Minneapolis, Minnesota 55455, USA. iadec001@tc.umn.edu

ABSTRACT
The transcription factor interferon regulatory factor 1 (IRF-1) is involved in the molecular mechanisms of inflammation and apoptosis, processes that contribute to ischemic brain injury. In this study, the induction of IRF-1 in response to cerebral ischemia and its role in ischemic brain injury were investigated. IRF-1 gene expression was markedly upregulated within 12 h of occlusion of the middle cerebral artery in C57BL/6 mice. The expression reached a peak 4 d after ischemia (6.0 +/- 1.8-fold; P < 0.001) and was restricted to the ischemic regions of the brain. The volume of ischemic injury was reduced by 23 +/- 3% in IRF-1(+/-) and by 46 +/- 9% in IRF-1(-/-) mice (P < 0.05). The reduction in infarct volume was paralleled by a substantial attenuation in neurological deficits. Thus, IRF-1 is the first nuclear transacting factor demonstrated to contribute directly to cerebral ischemic damage and may be a novel therapeutic target in ischemic stroke.

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IRF-1 mRNA expression in cerebral cortex of C57BL/6, IRF-1+/− and IRF-1−/− mice 4 d after MCA occlusion. Levels of IRF-1 mRNA  were determined as described in the legend to Fig. 1. (A) Representative  Southern blot with three individual mice per group illustrating IRF-1  mRNA expression in wild-type, IRF-1+/−, and IRF-1−/− mice. mRNA for  the housekeeping gene HPRT is shown as a control. (B) Group data illustrating IRF-1 mRNA expression in C57BL/6, IRF-1+/−, and IRF-1−/−  mice. Means (n = 5/group) are expressed as fold increase relative to the response observed in the nonischemic side (▪) of C57BL/6 mice. IRF-1  mRNA is reduced in IRF-1+/− mice and is absent in IRF-1−/−.
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Figure 2: IRF-1 mRNA expression in cerebral cortex of C57BL/6, IRF-1+/− and IRF-1−/− mice 4 d after MCA occlusion. Levels of IRF-1 mRNA were determined as described in the legend to Fig. 1. (A) Representative Southern blot with three individual mice per group illustrating IRF-1 mRNA expression in wild-type, IRF-1+/−, and IRF-1−/− mice. mRNA for the housekeeping gene HPRT is shown as a control. (B) Group data illustrating IRF-1 mRNA expression in C57BL/6, IRF-1+/−, and IRF-1−/− mice. Means (n = 5/group) are expressed as fold increase relative to the response observed in the nonischemic side (▪) of C57BL/6 mice. IRF-1 mRNA is reduced in IRF-1+/− mice and is absent in IRF-1−/−.

Mentions: We first sought to determine if focal cerebral ischemia enhances IRF-1 mRNA expression. In C57BL/6 mice, MCA occlusion was associated with pronounced upregulation of IRF-1 mRNA in the postischemic brain (Fig. 1). IRF-1 mRNA expression was increased by 12 h and remained elevated 1–7 d after MCA occlusion (P < 0.05 from sham-operated mice; analysis of variance and Tukey's test). IRF-1 mRNA expression did not increase in the contralateral (nonischemic) cortex (P > 0.05) (Fig. 1). IRF-1 mRNA expression was reduced in IRF-1+/− mice and absent in IRF-1−/− mice (Fig. 2).


The transcription factor interferon regulatory factor 1 is expressed after cerebral ischemia and contributes to ischemic brain injury.

Iadecola C, Salkowski CA, Zhang F, Aber T, Nagayama M, Vogel SN, Ross ME - J. Exp. Med. (1999)

IRF-1 mRNA expression in cerebral cortex of C57BL/6, IRF-1+/− and IRF-1−/− mice 4 d after MCA occlusion. Levels of IRF-1 mRNA  were determined as described in the legend to Fig. 1. (A) Representative  Southern blot with three individual mice per group illustrating IRF-1  mRNA expression in wild-type, IRF-1+/−, and IRF-1−/− mice. mRNA for  the housekeeping gene HPRT is shown as a control. (B) Group data illustrating IRF-1 mRNA expression in C57BL/6, IRF-1+/−, and IRF-1−/−  mice. Means (n = 5/group) are expressed as fold increase relative to the response observed in the nonischemic side (▪) of C57BL/6 mice. IRF-1  mRNA is reduced in IRF-1+/− mice and is absent in IRF-1−/−.
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Related In: Results  -  Collection

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Figure 2: IRF-1 mRNA expression in cerebral cortex of C57BL/6, IRF-1+/− and IRF-1−/− mice 4 d after MCA occlusion. Levels of IRF-1 mRNA were determined as described in the legend to Fig. 1. (A) Representative Southern blot with three individual mice per group illustrating IRF-1 mRNA expression in wild-type, IRF-1+/−, and IRF-1−/− mice. mRNA for the housekeeping gene HPRT is shown as a control. (B) Group data illustrating IRF-1 mRNA expression in C57BL/6, IRF-1+/−, and IRF-1−/− mice. Means (n = 5/group) are expressed as fold increase relative to the response observed in the nonischemic side (▪) of C57BL/6 mice. IRF-1 mRNA is reduced in IRF-1+/− mice and is absent in IRF-1−/−.
Mentions: We first sought to determine if focal cerebral ischemia enhances IRF-1 mRNA expression. In C57BL/6 mice, MCA occlusion was associated with pronounced upregulation of IRF-1 mRNA in the postischemic brain (Fig. 1). IRF-1 mRNA expression was increased by 12 h and remained elevated 1–7 d after MCA occlusion (P < 0.05 from sham-operated mice; analysis of variance and Tukey's test). IRF-1 mRNA expression did not increase in the contralateral (nonischemic) cortex (P > 0.05) (Fig. 1). IRF-1 mRNA expression was reduced in IRF-1+/− mice and absent in IRF-1−/− mice (Fig. 2).

Bottom Line: The transcription factor interferon regulatory factor 1 (IRF-1) is involved in the molecular mechanisms of inflammation and apoptosis, processes that contribute to ischemic brain injury.The reduction in infarct volume was paralleled by a substantial attenuation in neurological deficits.Thus, IRF-1 is the first nuclear transacting factor demonstrated to contribute directly to cerebral ischemic damage and may be a novel therapeutic target in ischemic stroke.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurology, University of Minnesota, Minneapolis, Minnesota 55455, USA. iadec001@tc.umn.edu

ABSTRACT
The transcription factor interferon regulatory factor 1 (IRF-1) is involved in the molecular mechanisms of inflammation and apoptosis, processes that contribute to ischemic brain injury. In this study, the induction of IRF-1 in response to cerebral ischemia and its role in ischemic brain injury were investigated. IRF-1 gene expression was markedly upregulated within 12 h of occlusion of the middle cerebral artery in C57BL/6 mice. The expression reached a peak 4 d after ischemia (6.0 +/- 1.8-fold; P < 0.001) and was restricted to the ischemic regions of the brain. The volume of ischemic injury was reduced by 23 +/- 3% in IRF-1(+/-) and by 46 +/- 9% in IRF-1(-/-) mice (P < 0.05). The reduction in infarct volume was paralleled by a substantial attenuation in neurological deficits. Thus, IRF-1 is the first nuclear transacting factor demonstrated to contribute directly to cerebral ischemic damage and may be a novel therapeutic target in ischemic stroke.

Show MeSH
Related in: MedlinePlus