Journal
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
Volume 390, Issue 3, Pages 678-683Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbrc.2009.10.027
Keywords
TLRs; TRIF; Cerebral ischemia/reperfusion; Mouse
Categories
Funding
- AHA National Program [SDG 0830481N]
- Emory University URC [2009-002]
- Department of Pediatric Cardiovascular Surgery at the Children's Hospital of Atlanta
- NIH [R01 NS04851]
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TIR domain-containing adaptor protein (TRIF) is an adaptor protein in Toll-like receptor (TLR) signaling pathways. Activation of TRIF leads to the activation of interferon regulatory factor 3 (IRF3) and nuclear factor kappa B (NF-kappa B). While studies have shown that TLRs are implicated in cerebral ischemia/reperfusion (I/R) injury and in neuroprotection against ischemia afforded by preconditioning, little is known about TRIF's role in the pathological process following cerebral I/R. The present study investigated the role that TRIF may play in acute cerebral I/R injury. In a mouse model of cerebral I/R induced by transient middle cerebral artery occlusion, we examined the activation of NF-kappa B and IRF3 signaling in ischemic cerebral tissue using ELISA and Western blots. Neurological function and cerebral infarct size were also evaluated 24 h after cerebral I/R. NF-kappa B activity and phosphorylation of the inhibitor of kappa B (I kappa B alpha) increased in ischemic brains, but IRF3, inhibitor of kappa B kinase complex-epsilon (IKK epsilon), and TANK-binding kinase1 (TBK1) were not activated after cerebral I/R in wild-type (WT) mice. Interestingly, TRIF deficit did not inhibit NF-kappa B activity or p-I kappa B alpha induced by cerebral I/R. Moreover, although cerebral I/R induced neurological and functional impairments and brain infarction in WT mice, the deficits were not improved and brain infarct size was not reduced in TRIF knockout mice compared to WT mice. Our results demonstrate that the TRIF-dependent signaling pathway is not required for the activation of NF-kappa B signaling and brain injury after acute cerebral I/R. (C) 2009 Elsevier Inc. All rights reserved.
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