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2009 | 69 | 3 |
Tytuł artykułu

The HMGB1 receptor rage mediates ischemic brain damage

Warianty tytułu
Języki publikacji
EN
Abstrakty
EN
In ischemic stroke, the necrotic core is surrounded by a zone of infl ammation, in which delayed cell death aggravates the initial insult. Here, we provide evidence that the receptor for advanced glycation end products (RAGE) functions as a sensor of necrotic cell death and contributes to infl ammation and ischemic brain damage. The RAGE ligand high mobility group box 1 (HMGB1) was elevated in serum of stroke patients and was released from ischemic brain tissue in a mouse model of cerebral ischemia. A neutralizing anti-HMGB1 antibody and HMGB1 box A, an antagonist of HMGB1 at the receptor RAGE, ameliorated ischemic brain damage. Interestingly, genetic RAGE defi ciency and the decoy receptor soluble RAGE (sRAGE) reduced the infarct size. In vitro, expression of RAGE in (micro)glial cells mediated the toxic effect of HMGB1. Addition of macrophages to neural cultures further enhanced the toxic effect of HMGB1. To test whether immigrant macrophages in the ischemic brain mediate the RAGE effect, we generated chimeric mice by transplanting RAGE-/- bone marrow to wild-type mice. RAGE defi ciency in bone marrow-derived cells signifi cantly reduced the infarct size. Thus, HMGB1-RAGE signaling links necrosis with macrophage activation and may provide a target for anti-infl ammatory therapy in stroke.
Słowa kluczowe
Wydawca
-
Rocznik
Tom
69
Numer
3
Opis fizyczny
p.310-311
Twórcy
autor
  • Pharmacological Institute, University of Heidelberg, Heidelberg, Germany
autor
  • Pharmacological Institute, University of Heidelberg, Heidelberg, Germany
autor
  • Department of Internal Medicine, University of Heidelberg, Heidelberg, Germany
autor
  • Pharmacological Institute, University of Heidelberg, Heidelberg, Germany
autor
  • Feinstein Institute for Medical Research, Manhasset, USA
autor
  • Feinstein Institute for Medical Research, Manhasset, USA
autor
  • Department Neuroradiology, University of Heidelberg, Heidelberg, Germany
autor
  • HMGBiotech, Milan, Italy
  • Department of Internal Medicine, University of Heidelberg, Heidelberg, Germany
autor
  • Department of Internal Medicine, University of Heidelberg, Heidelberg, Germany
  • Pharmacological Institute, University of Heidelberg, Heidelberg, Germany
Bibliografia
Typ dokumentu
Bibliografia
Identyfikatory
Identyfikator YADDA
bwmeta1.element.agro-9f0c0d2b-a04d-4603-9a85-95ace5bbdc1d
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