Overexpression of heat shock protein 72 attenuates NF-κB activation using a combination of regulatory mechanisms in microglia.

ABSTRACT: Overexpression of the inducible heat shock protein 70, Hsp72, has broadly cytoprotective effects and improves outcome following stroke. A full understanding of how Hsp72 protects cells against injury is elusive, though several distinct mechanisms are implicated. One mechanism is its anti-inflammatory effects. We study the effects of Hsp72 overexpression on activation of the transcription factor NF-κB in microglia combining experimentation and mathematical modeling, using TNFα to stimulate a microglial cell line stably overexpressing Hsp72. We find that Hsp72 overexpression reduces the amount of NF-κB DNA binding activity, activity of the upstream kinase IKK, and amount of IκBα inhibitor phosphorylated following TNFα application. Simulations evaluating several proposed mechanisms suggest th

SUBMITTER: Sheppard PW 

PROVIDER: S-EPMC3916226 | biostudies-literature | 2014 Feb

REPOSITORIES: biostudies-literature