Protective Effect of Piceatannol Against Acute Lung Injury Through Protecting the Integrity of Air-Blood Barrier and Modulating the TLR4/NF-κB Signaling Pathway Activation

Abstract

Acute lung injury (ALI) is a common and complex inflammatory lung syndrome with higher morbidity and mortality rate. Piceatannol (PIC) has anti-inflammation and anti-oxidant properties. The study was designed to explore the effect and the action mechanisms of PIC on lipopolysaccharide (LPS)-induced ALI. Twenty-four hours after LPS challenge, mice from different treatment groups were euthanized, and the bronchoalveolar lavage fluid (BALF) and lung tissue samples were collected. Then the degree of pulmonary edema, lung pathological changes, myeloperoxidase (MPO) activity, and the production of pro-inflammatory cytokines were detected. Additionally, the messenger RNA (mRNA) expressions associated with cell adhesion molecules and tight junction were analyzed through quantitative real-time (qRT)-PCR, and the TLR4/NF-kB activation was examined by western blot. The results showed that PIC significantly inhibited LPS-induced lung edema, histopathological damage, MPO activity, cell infiltration, and pro-inflammatory cytokines production. Moreover, PIC notably suppressed mRNA expressions associated with inflammation and cell adhesion molecules. Furthermore, PIC also alleviated LPSinduced damage of air-blood barrier through reducing the levels of total proteins in BALF and recovering the expression of occludin and ZO-1 in the lung tissues. We also found that PIC remarkably restrained the LPS-induced TLR4/NF-kB pathway activation in lung tissues. In conclusion, PIC may be potential to treat LPS-induced acute lung injury (ALI) via regulating air-blood barrier and TLR4/NF-kB signaling pathway activation.

COLEC12 regulates apoptosis of osteosarcoma through Toll‐like receptor 4–activated inflammation

“…MPO activity is always regarded as a reflection of neutrophil infiltration, which is related to TLR4/NF-κB signaling pathway. 27 In our study, the increasing level of MPO, complement C3, and inflammatory factors by COLEC12 knockdown could further describe the immunomodulatory function of COLEC12.…”

“…Our findings show that immunofluorescence staining of MPO and TLR4, NF‐κB, IL‐1β, IL‐18, TNF‐α, and C3 protein levels was increased by COLEC12 knockdown. MPO activity is always regarded as a reflection of neutrophil infiltration, which is related to TLR4/NF‐κB signaling pathway 27 . In our study, the increasing level of MPO, complement C3, and inflammatory factors by COLEC12 knockdown could further describe the immunomodulatory function of COLEC12.…”

Identification and Functional Analysis of Long Non-coding RNAs in Human Pulmonary Microvascular Endothelial Cells Subjected to Cyclic Stretch

“…It has been reported that TNFAIP3 may stabilize the endothelial barrier by regulating the expression of VE-cadherin in acute lung injury (ALI) (Soni et al, 2018 ). Previous studies have also indicated that endothelial cells-expressed TLR4 increased vascular permeability and inflammatory responses in the early stages of ALI and/or ARDS (Tauseef et al, 2012 ; Wu et al, 2017 ; Peng et al, 2019 ). Its mechanism of action was likely to be that TLR4 induced the immune response by activating NF-κB signaling pathway via phosphorylating IRAK1 and IRAK2.…”

Regulation of PINX1 expression ameliorates lipopolysaccharide-induced lung injury and alleviates cell senescence during the convalescent phase through affecting the telomerase activity

“…Sepsis is a systemic inflammatory response syndrome caused by infection, which increases the incidence and mortality of several organ injuries [ 1 ]. Acute lung injury (ALI) is one of the most common complications of sepsis resulting from pulmonary susceptibility [ 2 ]. ALI, a critical syndrome with worryingly high morbidity and mortality in intensive care patients, leads to edema, hypoxemia, and even acute respiratory distress syndrome (ARDS) [ 3 , 4 ].…”