Phospho-Tyr705 of STAT3 is a therapeutic target for sepsis through regulating inflammation and coagulation.

ABSTRACT:

Background

Sepsis is an infection-induced aggressive and life-threatening organ dysfunction with high morbidity and mortality worldwide. Infection-associated inflammation and coagulation promote the progression of adverse outcomes in sepsis. Here, we report that phospho-Tyr705 of STAT3 (pY-STAT3), not total STAT3, contributes to systemic inflammation and coagulopathy in sepsis.

Methods

Cecal ligation and puncture (CLP)-induced septic mice were treated with BP-1-102, Napabucasin, or vehicle control respectively and then assessed for systemic inflammation, coagulation response, lung function and survival. Human pulmonary microvascular endothelial cells (HPMECs) and Raw264.7 cells were exposed to lipopolysaccharide (LPS) with pharmacological or genetic inhibition of pY-STAT3. C

SUBMITTER: Xu S 

PROVIDER: S-EPMC7341624 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature