The Journal of Experimental Medicine
  Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents
This Article
Right arrow Full Text
Right arrow Full Text (PDF, 177K)
Right arrow PPT slides of all figures
Right arrow Alert me when this article is cited
Right arrow Citation Map
Services
Right arrow Email this article
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new content in the JEM
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via CrossRef
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Iadecola, C.
Right arrow Articles by Elizabeth Ross, M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Iadecola, C.
Right arrow Articles by Elizabeth Ross, M.
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Facebook   Add to Reddit   Add to Technorati   Add to Twitter  
What's this?
© The Rockefeller University Press, 0022-1007/1999/2/719/ $5.00
The Journal of Experimental Medicine, Volume 189, Number 4, February 15, 1999 719-727

Articles

The Transcription Factor Interferon Regulatory Factor 1 Is Expressed after Cerebral Ischemia and Contributes to Ischemic Brain Injury

Costantino Iadecola*, Cindy A. Salkowski{ddagger}, Fangyi Zhang*, Tracy Aber*, Masao Nagayama*, Stefanie N. Vogel{ddagger}, and M. Elizabeth Ross*

From the * Department of Neurology, University of Minnesota, Minneapolis, Minnesota 55455; and the {ddagger} Department of Microbiology and Immunology, Uniformed Services University of the Health Sciences, Bethesda, Maryland 20814

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.

Key Words: cerebral ischemia • interferon regulatory factor 1 null mice • gene expression • neuroprotection • reverse transcription polymerase chain reaction

Address correspondence to Costantino Iadecola, Department of Neurology, University of Minnesota, Box 295 UMHC, 420 Delaware St. South-East, Minneapolis, MN 55455. Phone: 612-624-1902; Fax: 612-625-7950; E-mail: iadec001{at}tc.umn.edu

The excellent editorial assistance of Ms. Karen MacEwan is acknowledged. We wish to thank Ms. Diana Miller for technical assistance.

Abbreviations used: CBF, cerebral blood flow; HPRT, hypoxanthine-guanine phosphoribosyl transferase; IRF-1, interferon regulatory factor 1, iNOS, inducible nitric oxide synthase; MCA, middle cerebral artery; NO, nitric oxide.


Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Facebook Facebook   Add to Reddit Reddit   Add to Technorati Technorati   Add to Twitter Twitter    What's this?


This article has been cited by other articles:



  Home | Help | Feedback | Subscriptions | Archive | Search
TABLE OF CONTENTS