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• W1983402893 abstract "Double-stranded RNA dependent protein kinase (PKR) is a host defense enzyme whose expression is up-regulated in response to interferons (IFNs) and during viral infections. Increased levels of PKR can result in its activation, which, in turn, inhibits global cellular protein synthesis. Despite growing evidence suggesting the involvement of PKR in bacterial infections, little is known about its expression, regulation and cellular role in nonviral infections. The aim of this work was to determine the expression and regulation of PKR in response to stimulation of human THP-1 monocytes with bacterial agonists of TLR2/4. Treatment of cells with Pam3CSK4 or lipopolyssacharide (LPS) resulted in an increase in PKR mRNA and protein levels. Robust PKR expression at later times correlated with a decrease in global protein synthesis. PKR was also required to regulate the inhibition of protein synthesis triggered by LPS in mouse splenocytes. Surprisingly, no increase of IFN-β or IFN-α mRNA levels was detected after treatment of THP-1 cells with toll-like receptor (TLR) agonists. In accordance with this, the supernatants from LPS or Pam3CSK4-treated cells lacked the ability to activate the PKR and ISG56 promoters in gene reporter assays carried out in HEK293T cells. The expression of PKR induced by TLRs agonists was dramatically impaired when cells were treated in the presence of tosyl-phenylalanyl chloromethylketone or Mithramycin, suggesting that NF-κB and Sp1 transcription factors, but not those activated by IFNs, regulate the expression of PKR in human monocytes." @default.
• W1983402893 created "2016-06-24" @default.
• W1983402893 creator A5022693875 @default.
• W1983402893 creator A5065957840 @default.
• W1983402893 creator A5081150848 @default.
• W1983402893 date "2012-10-01" @default.
• W1983402893 modified "2023-10-05" @default.
• W1983402893 title "Regulation of Double-Stranded RNA Dependent Protein Kinase Expression and Attenuation of Protein Synthesis Induced by Bacterial Toll-Like Receptors Agonists in the Absence of Interferon" @default.
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• W1983402893 doi "https://doi.org/10.1089/jir.2012.0019" @default.
• W1983402893 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/22873641" @default.
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