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Toll-Like Receptor 2 Deficiency Shifts PrP106-126-Induced Microglial Activation from a Neurotoxic to a Neuroprotective Phenotype.
MedLine Citation:
PMID:  25330861     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Prion diseases are fatal neurodegenerative diseases characterized by spongiform change, neuronal loss, and gliosis involving microglial activation in the central nervous system. Microglial activation is thought to play a key role in the pathogenesis of prion disease; however, the molecular mechanisms underlying prion-induced microglial activation are not well understood. The present study underlines the importance of toll-like receptor (TLR)-2 in mediating PrP106-126-induced microglial activation. We found that PrP106-126 induced expression of proinflammatory molecules and TLR2 in microglial cells; however, functional blocking antibodies against TLR2 suppressed PrP106-126-induced expression of proinflammatory molecules. PrP106-126-induced expression of proinflammatory molecules was also reduced in microglial cells isolated from TLR2-/- mice compared to those isolated from wild-type mice. Consistent with the importance of nuclear factor kappa B (NF-κB) mediating TLR functions, NF-κB inhibition also inhibited PrP106-126-induced expression of proinflammatory molecules. To better understand the effect of TLR2 deficiency on active microglial cells, we studied the expression of Arg1 and Mrc1 and anti-inflammatory cytokines, which indicated that TLR2 deficiency in microglial cells results in a shift from neurotoxic to neuroprotective phenotype. Taken together, our results indicate that the TLR2 signaling pathway mediates PrP106-126-induced microglial activation and potentially reveal new therapeutic strategies for prion diseases that modulate TLR2 signaling.
Authors:
Jihong Wang; Deming Zhao; Bo Pan; Yongyao Fu; Fushan Shi; Mohammed Kouadir; Lifeng Yang; Xiaomin Yin; Xiangmei Zhou
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2014-10-21
Journal Detail:
Title:  Journal of molecular neuroscience : MN     Volume:  -     ISSN:  1559-1166     ISO Abbreviation:  J. Mol. Neurosci.     Publication Date:  2014 Oct 
Date Detail:
Created Date:  2014-10-21     Completed Date:  -     Revised Date:  2014-10-22    
Medline Journal Info:
Nlm Unique ID:  9002991     Medline TA:  J Mol Neurosci     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
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