An Endothelial Hsp70-TLR4 Axis Limits Nox3 Expression and Protects Against Oxidant Injury in Lungs.

ABSTRACT:

Aims

Oxidants play a critical role in the pathogenesis of acute lung injury (ALI). Nox3 is a novel member of the NADPH oxidase (Nox) family of oxidant-generating enzymes, which our laboratory had previously identified to be induced in the lungs of TLR4(-/-) mice. However, the physiologic role of Nox3 induction in lungs and its precise relationship to TLR4 are unknown. Furthermore, the cell compartment involved and the signaling mechanisms of Nox3 induction are unknown.

Results

We identified that Nox3 is regulated by heat shock protein 70 (Hsp70) signaling via a TLR4-Trif-signal transducer and activator of transcription 3 (Stat3) pathway and that Nox3 induction leads to increased oxidant injury and death in mice and lung endothelial cells. We generated Nox3(-/-)/TLR4(-/-) dou

SUBMITTER: Zhang Y 

PROVIDER: S-EPMC4922010 | biostudies-literature | 2016 Jun

REPOSITORIES: biostudies-literature