RGD Reference Report - TLR2 ligand induces protection against cerebral ischemia/reperfusion injury via activation of phosphoinositide 3-kinase/Akt signaling. - Rat Genome Database
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TLR2 ligand induces protection against cerebral ischemia/reperfusion injury via activation of phosphoinositide 3-kinase/Akt signaling.

Authors: Lu, C  Liu, L  Chen, Y  Ha, T  Kelley, J  Schweitzer, J  Kalbfleisch, JH  Kao, RL  Williams, DL  Li, C 
Citation: Lu C, etal., J Immunol. 2011 Aug 1;187(3):1458-66. Epub 2011 Jun 27.
RGD ID: 6218961
Pubmed: (View Article at PubMed) PMID:21709150
DOI: Full-text: DOI:10.4049/jimmunol.1003428

This study examined the effect of TLR2 activation by its specific ligand, Pam3CSK4, on cerebral ischemia/reperfusion (I/R) injury. Mice (n = 8/group) were treated with Pam3CSK4 1 h before cerebral ischemia (60 min), followed by reperfusion (24 h). Pam3CSK4 was also given to the mice (n = 8) 30 min after ischemia. Infarct size was determined by triphenyltetrazolium chloride staining. The morphology of neurons in brain sections was examined by Nissl staining. Pam3CSK4 administration significantly reduced infarct size by 55.9% (p < 0.01) compared with untreated I/R mice. Therapeutic treatment with Pam3CSK4 also significantly reduced infarct size by 55.8%. Morphologic examination showed that there was less neuronal damage in the hippocampus of Pam3CSK4-treated mice compared with untreated cerebral I/R mice. Pam3CSK4 treatment increased the levels of Hsp27, Hsp70, and Bcl2, and decreased Bax levels and NF-kappaB-binding activity in the brain tissues. Administration of Pam3CSK4 significantly increased the levels of phospho-Akt/Akt and phospho-GSK-3beta/GSK-3beta compared with untreated I/R mice. More significantly, either TLR2 deficiency or PI3K inhibition with LY29004 abolished the protection by Pam3CSK4. These data demonstrate that activation of TLR2 by its ligand prevents focal cerebral ischemic damage through a TLR2/PI3K/Akt-dependent mechanism. Of greater significance, these data indicate that therapy with a TLR2-specific agonist during cerebral ischemia is effective in reducing injury.

Annotation

Disease Annotations    

Objects Annotated

Genes (Rattus norvegicus)
Hspa4  (heat shock protein family A (Hsp70) member 4)

Genes (Mus musculus)
Hspa4  (heat shock protein 4)

Genes (Homo sapiens)
HSPA4  (heat shock protein family A (Hsp70) member 4)


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