Telomere Protection Protein 1 (TPP1) Deletion in Lung Epithelial Cells Augments Cigarette Smoke-Induced Lung Inflammation

Caspases have been implicated in the effector process of apoptosis in several systems including the Fas-Fas ligand pathway. We previously demonstrated that excessive apoptosis of lung epithelial cells and the Fas-Fas ligand pathway were essential in the pathogenesis of bleomycin-induced pneumopathy in mice. Therefore, the purpose of this study was to investigate whether a caspase inhibitor could prevent the development of this model. The expression of caspase-1 and caspase-3 was upregulated on lung epithelial cells, alveolar macrophages, and infiltrating inflammatory cells in this model. We demonstrated that a broad-spectrum caspase inhibitor, N-benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone, decreased the caspase-1- and caspase-3-like activity, the number of apoptotic cells, the pathological grade of lung inflammation and fibrosis, and the hydroxyproline content in lung tissues in this model. We conclude that caspase inhibitors could be a new therapeutic approach against lung injury and pulmonary fibrosis.

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Cigarette smoke extract increases mitochondrial membrane permeability through activation of adenine nucleotide translocator (ANT) in lung epithelial cells

Biochemical and Biophysical Research Communications ◽

10.1016/j.bbrc.2020.02.160 ◽

2020 ◽

Vol 525 (3) ◽

pp. 733-739 ◽

Cited By ~ 2

Author(s):

Kaiyue Wu ◽

Guangxin Luan ◽

Yanhong Xu ◽

Shuang Shen ◽

Shengnan Qian ◽

...

Keyword(s):

Epithelial Cells ◽

Membrane Permeability ◽

Cigarette Smoke ◽

Mitochondrial Membrane ◽

Adenine Nucleotide ◽

Cigarette Smoke Extract ◽

Lung Epithelial Cells ◽

Adenine Nucleotide Translocator ◽

Mitochondrial Membrane Permeability ◽

Lung Epithelial

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Down-Regulation of p23 in Normal Lung Epithelial Cells Reduces Toxicities From Exposure to Benzo[a]pyrene and Cigarette Smoke Condensate via an Aryl Hydrocarbon Receptor-Dependent Mechanism

Toxicological Sciences ◽

10.1093/toxsci/kfy234 ◽

2018 ◽

Vol 167 (1) ◽

pp. 239-248 ◽

Cited By ~ 3

Author(s):

Jinyun Chen ◽

Poonam Yakkundi ◽

William K Chan

Keyword(s):

Epithelial Cells ◽

Aryl Hydrocarbon Receptor ◽

Cigarette Smoke ◽

Lung Epithelial Cells ◽

Normal Lung ◽

Cigarette Smoke Condensate ◽

Down Regulation ◽

Protein Levels ◽

Aryl Hydrocarbon ◽

Lung Epithelial

Abstract The aryl hydrocarbon receptor (AHR) is a ligand-activated signaling molecule which controls tumor growth and metastasis, T cell differentiation, and liver development. Expression levels of this receptor protein is sensitive to the cellular p23 protein levels in immortalized cancer cell lines. As little as 30% reduction of the p23 cellular content can suppress the AHR function. Here we reported that down-regulation of the p23 protein content in normal, untransformed human bronchial/tracheal epithelial cells to 48% of its content also suppresses the AHR protein levels to 54% of its content. This p23-mediated suppression of AHR is responsible for the suppression of (1) the ligand-dependent induction of the cyp1a1 gene transcription; (2) the benzo[a]pyrene- or cigarette smoke condensate-induced CYP1A1 enzyme activity, and (3) the benzo[a]pyrene and cigarette smoke condensate-mediated production of reactive oxygen species. Reduction of the p23 content does not alter expression of oxidative stress genes and production of PGE2. Down regulation of p23 suppresses the AHR protein levels in two other untransformed cell types, namely human breast MCF-10A and mouse immune regulatory Tr1 cells. Collectively, down-regulation of p23 suppresses the AHR protein levels in normal and untransformed cells and can in principle protect our lung epithelial cells from AHR-dependent oxidative damage caused by exposure to agents from environment and cigarette smoking.

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