Protein Kinase R Mediates the Inflammatory Response Induced by Hyperosmotic Stress.
Mol Cell Biol
; 37(4)2017 02 15.
Article
in En
| MEDLINE
| ID: mdl-27920257
ABSTRACT
High extracellular osmolarity results in a switch from an adaptive to an inflammatory gene expression program. We show that hyperosmotic stress activates the protein kinase R (PKR) independently of its RNA-binding domain. In turn, PKR stimulates nuclear accumulation of nuclear factor κB (NF-κB) p65 species phosphorylated at serine-536, which is paralleled by the induction of a subset of inflammatory NF-κB p65-responsive genes, including inducible nitric oxide synthase (iNOS), interleukin-6 (IL-6), and IL-1ß. The PKR-mediated hyperinduction of iNOS decreases cell survival in mouse embryonic fibroblasts via mechanisms involving nitric oxide (NO) synthesis and posttranslational modification of proteins. Moreover, we demonstrate that the PKR inhibitor C16 ameliorates both iNOS amplification and disease-induced phenotypic breakdown of the intestinal epithelial barrier caused by an increase in extracellular osmolarity induced by dextran sodium sulfate (DSS) in vivo Collectively, these findings indicate that PKR activation is an essential part of the molecular switch from adaptation to inflammation in response to hyperosmotic stress.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Osmotic Pressure
/
EIF-2 Kinase
/
Inflammation
Limits:
Animals
Language:
En
Journal:
Mol Cell Biol
Year:
2017
Document type:
Article
Affiliation country:
Estados Unidos