Alveolar epithelial inter-alpha-trypsin inhibitor heavy chain 4 deficiency associated with senescence-regulated apoptosis by air pollution
Journal
Environmental Pollution
Journal Volume
278
Date Issued
2021
Author(s)
Chen X.-Y
Abstract
Capsule of main finding: The significance and novelty of this study are that ITIH4 regulates alveolar cell destruction by air pollution and thus could be an indicator of lung injury due to air pollution. ? 2021 Elsevier LtdInter-alpha-trypsin inhibitor heavy chain 4 (ITIH4) is a type II acute-phase protein; however, the role of pulmonary ITIH4 after exposure to air pollution remains unclear. In this study, we investigated the role of ITIH4 in the lungs in response to air pollution. ITIH4 expression in bronchoalveolar lavage fluid (BAL) of 47 healthy human subjects and of Sprague-Dawley rats whole-body exposed to air pollution was determined, and the underlying antiapoptotic and matrix-stabilizing pathways in alveolar epithelial A549 cells induced by diesel exhaust particles (DEPs) as well as ITIH4-knockdown were investigated. We found that an interquartile range (IQR) increase in PM2.5 was associated with a decrease of 2.673 ng/mL in ITIH4, an increase of 1.104 pg/mL of 8-isoprostane, and an increase of 6.918 pg/mL of interleukin (IL)-6 in human BAL. In rats, increases in 8-isoprostane, IL-6, and p53 and a decrease in sirtuin-1 (Sirt1) in the lungs and decreases in ITIH4 in the BAL, lungs, and serum were observed after PM2.5 and gaseous exposure. ITIH4 levels in lung lysates were correlated with levels in BAL samples (r = 0.377, p < 0.01), whereas ITIH4 levels in BAL were correlated with IL-6 levels (r = ?0.420, p < 0.01). ITIH4 expression was significantly reduced in alveolar epithelial A549 cells by DEP in a dose-dependent manner. A decrease in Sirt1 and increases in phosphorylated extracellular signal-regulated kinase (p-ERK) and caspase-3 were observed after DEP exposure and ITIH4-knockdown. In conclusion, air pollution decreased ITIH4 expression in the lungs, which was associated with alveolar epithelial cell senescence and apoptosis. ITIH4 could be a vital protein in regulating alveolar cell destruction and its inhibition after exposure to air pollution. ? 2021 Elsevier Ltd
Subjects
Air pollution; Cell death; Proteins; Rats; A549 cells; Bronchoalveolar lavage fluid; Cell destruction; Diesel exhaust particles; Heavy chain; Interleukin6 (IL6); Particulate Matter; PM$-2.5$; Sirtuin-1; Trypsin inhibitor; Oxidative stress; 8 isoprostane; acute phase protein; caspase 3; diesel fuel; inter alpha trypsin inhibitor; inter alpha trypsin inhibitor heavy chain 4; interleukin 6; mitogen activated protein kinase; protein p53; sirtuin 1; unclassified drug; alpha globulin; inter-alpha-inhibitor; apoptosis; atmospheric pollution; gene expression; inhibitor; oxidative stress; particulate matter; pollution exposure; A-549 cell line; adult; air pollution; animal cell; animal experiment; animal model; animal tissue; apoptosis; Article; blood analysis; bronchoalveolar lavage fluid; cell aging; cell destruction; concentration response; controlled study; correlation analysis; diesel particulate matter; environmental exposure; enzyme phosphorylation; female; gene silencing; human; human cell; human tissue; lung alveolus epithelium; lung parenchyma; male; middle aged; nonhuman; normal human; particulate matter 2.5; protein deficiency; protein expression; protein function; rat; Sprague Dawley rat; volunteer; adverse event; animal; apoptosis; exhaust gas; Indicator indicator; Air Pollution; Alpha-Globulins; Animals; Apoptosis; Rats; Rats, Sprague-Dawley; Vehicle Emissions
Other Subjects
Air pollution; Cell death; Proteins; Rats; A549 cells; Bronchoalveolar lavage fluid; Cell destruction; Diesel exhaust particles; Heavy chain; Interleukin6 (IL6); Particulate Matter; PM$-2.5$; Sirtuin-1; Trypsin inhibitor; Oxidative stress; 8 isoprostane;
Type
journal article