Indole-3-acetic acid protected against LPS-induced endothelial dysfunction and acute lung injury through activation of USP40.
Indole-3-acetic acid protects against LPS-induced endothelial dysfunction and acute lung injury by activating USP40 to deubiquitinate HSP90β.
Abstract Rationale Lung microvascular endothelial cell (EC) dysfunction is the pathological hallmark of acute respiratory distress syndrome. Hsp90 plays a central role in mediating endothelial cell inflammation and barrier dysfunction in response to endotoxin exposure. Our findings demonstrate that ubiquitin-specific peptidase 40 (USP40) maintains endothelial integrity by deubiquitinating the heat shock protein HSP90β. Indole-3-acetic acid (IAA) is the most common naturally occurring plant hormone of the auxin class. Accumulating evidence suggests that IAA reduces oxidative stress and inflammation and promotes intestinal barrier function. However, little is known about the role of IAA in endothelial cells and acute lung injury. Methods Endothelial barrier function in human lung microvascular endothelial cells (HLMVECs) was assessed via ECIS and TEER measurements. HEK293/TLR4 cells pretreated with 0.2 mM IAA (3h) underwent modified IP and ubiquitin immunoblotting. USP40 DUB activity with IAA was analyzed using Ub-AMC. Lung injury was induced by intratracheal lipopolysaccharide (LPS) (2 mg/kg, 24 h). BAL fluid and lung tissue were collected for ELISA, protein assay, H R01HL167846 and R01HL151513 to J. Zhao.
Shaheen et al. (Fri,) conducted a other in Acute respiratory distress syndrome / Acute lung injury. Indole-3-acetic acid (IAA) vs. LPS alone was evaluated on Endothelial barrier function and inflammation. Indole-3-acetic acid protected against LPS-induced endothelial dysfunction and acute lung injury through activation of USP40.