scholarly journals Genetic Ablation of NADPH Oxidase Enhances Susceptibility to Cigarette Smoke-Induced Lung Inflammation and Emphysema in Mice

2008 ◽  
Vol 172 (5) ◽  
pp. 1222-1237 ◽  
Author(s):  
Hongwei Yao ◽  
Indika Edirisinghe ◽  
Se-Ran Yang ◽  
Saravanan Rajendrasozhan ◽  
Aruna Kode ◽  
...  
Keyword(s):  
Nadph Oxidase ◽  
Cigarette Smoke ◽  
Lung Inflammation ◽  
Genetic Ablation

scholarly journals Lung Epithelial TRPA1 Transduces the Extracellular ROS into Transcriptional Regulation of Lung Inflammation Induced by Cigarette Smoke: The Role of Influxed Ca2+

2015 ◽  
Vol 2015 ◽  
pp. 1-16 ◽  
Author(s):  
An-Hsuan Lin ◽  
Meng-Han Liu ◽  
Hsin-Kuo Ko ◽  
Diahn-Warng Perng ◽  
Tzong-Shyuan Lee ◽  
...  
Keyword(s):  
Nadph Oxidase ◽  
Cigarette Smoke ◽  
Lung Inflammation ◽  
Lung Epithelial Cells ◽  
Wild Type ◽  
Intracellular Ros ◽  
Lung Epithelial ◽  
Intracellular Ca ◽  
Acetyl Cysteine

The mechanism underlying the inflammatory role of TRPA1 in lung epithelial cells (LECs) remains unclear. Here, we show that cigarette smoke extract (CSE) sequentially induced several events in LECs. The Ca2+influx was prevented by decreasing extracellular reactive oxygen species (ROS) with the scavenger N-acetyl-cysteine, removing extracellular Ca2+with the chelator EGTA, or treating with the TRPA1 antagonist HC030031. NADPH oxidase activation was abolished by its inhibitor apocynin, EGTA, or HC030031. The increased intracellular ROS was halted by apocynin, N-acetyl-cysteine, or HC030031. The activation of the MAPKs/NF-κB signaling was suppressed by EGTA, N-acetyl-cysteine, or HC030031. IL-8 induction was inhibited by HC030031 or TRPA1 siRNA. Additionally, chronic cigarette smoke (CS) exposure in wild-type mice induced TRPA1 expression in LECs and lung tissues. In CS-exposuretrpa1−/−mice, the increased BALF level of ROS was similar to that of CS-exposure wild-type mice; yet lung inflammation was lessened. Thus, in LECs, CSE may initially increase extracellular ROS, which activate TRPA1 leading to an increase in Ca2+influx. The increased intracellular Ca2+contributes to activation of NADPH oxidase, resulting in increased intracellular ROS, which activate the MAPKs/NF-κB signaling leading to IL-8 induction. This mechanism may possibly be at work in mice chronically exposed to CS.

Cigarette smoke extract amplifies NADPH oxidase-dependent ROS production to inactivate PTEN by oxidation in BEAS-2B cells

2021 ◽  
Vol 150 ◽  
pp. 112050
Author(s):  
Bangrong Cai ◽  
Mengya Liu ◽  
Jinxing Li ◽  
Dujuan Xu ◽  
Jiansheng Li
Keyword(s):  
Nadph Oxidase ◽  
Cigarette Smoke ◽  
Cigarette Smoke Extract ◽  
Ros Production

Effects of intranasal azithromycin on features of cigarette smoke-induced lung inflammation

2021 ◽  
pp. 174467
Author(s):  
Siddhi Jain ◽  
Sneha Durugkar ◽  
Pritam Saha ◽  
Sharad B. Gokhale ◽  
V.G.M. Naidu ◽  
...  
Keyword(s):  
Cigarette Smoke ◽  
Lung Inflammation

scholarly journals p53- and PAI-1-mediated induction of C-X-C chemokines and CXCR2: importance in pulmonary inflammation due to cigarette smoke exposure

2016 ◽  
Vol 310 (6) ◽  
pp. L496-L506 ◽  
Author(s):  
Nivedita Tiwari ◽  
Amarnath S. Marudamuthu ◽  
Yoshikazu Tsukasaki ◽  
Mitsuo Ikebe ◽  
Jian Fu ◽  
...  
Keyword(s):  
Lung Injury ◽  
Cigarette Smoke ◽  
Lung Inflammation ◽  
Cellular Adhesion ◽  
Alveolar Epithelial Cells ◽  
Cigarette Smoke Exposure ◽  
Chronic Obstructive ◽  
P53 Expression ◽  
Cellular Adhesion Molecule ◽  
Pai 1

We previously demonstrated that tumor suppressor protein p53 augments plasminogen activator inhibitor-1 (PAI-1) expression in alveolar epithelial cells (AECs) during chronic cigarette smoke (CS) exposure-induced lung injury. Chronic lung inflammation with elevated p53 and PAI-1 expression in AECs and increased susceptibility to and exacerbation of respiratory infections are all associated with chronic obstructive pulmonary disease (COPD). We recently demonstrated that preventing p53 from binding to the endogenous PAI-1 mRNA in AECs by either suppressing p53 expression or blockading p53 interactions with the PAI-1 mRNA mitigates apoptosis and lung injury. Within this context, we now show increased expression of the C-X-C chemokines (CXCL1 and CXCL2) and their receptor CXCR2, and the intercellular cellular adhesion molecule-1 (ICAM-1), in the lung tissues of patients with COPD. We also found a similar increase in lung tissues and AECs from wild-type (WT) mice exposed to passive CS for 20 wk and in primary AECs treated with CS extract in vitro. Interestingly, passive CS exposure of mice lacking either p53 or PAI-1 expression resisted an increase in CXCL1, CXCL2, CXCR2, and ICAM-1. Furthermore, inhibition of p53-mediated induction of PAI-1 expression by treatment of WT mice exposed to passive CS with caveolin-1 scaffolding domain peptide reduced CXCL1, CXCL2, and CXCR2 levels and lung inflammation. Our study reveals that p53-mediated induction of PAI-1 expression due to chronic CS exposure exacerbates lung inflammation through elaboration of CXCL1, CXCL2, and CXCR2. We further provide evidence that targeting this pathway mitigates lung injury associated with chronic CS exposure.

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