Ozone stress down-regulates the expression of cystic fibrosis transmembrane conductance regulator in human bronchial epithelial cells

Qü, Fei; Qin, Xiaoqun; Cui, Yanru; Xiang, Yang; Tan, Yurong; Liu, Huijun; Peng, Lihua; Zhou, Xiaoyan; Liu, Chi; Zhu, Xiaoguang

doi:10.1016/j.cbi.2008.10.059

Cited by 36 publications

(26 citation statements)

References 26 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These experiments illustrate new features concerning the role of Nrf2 in a non-cytoprotective gene and extended the interest of studying its role in the regulation of other genes. The repressive role of Nrf2 is consistent with other investigations, which showed that oxidative stress induced by various drugs or ozone suppressed the CFTR expression [10,11,41].…”

Section: Discussionsupporting

confidence: 80%

“…Using oxidants, Cantin et al [10] demonstrated that oxidative stress suppresses CFTR mRNA expression. Recently, ozone stress has also been shown to decrease CFTR expression in human airway epithelium [11]. However, the molecular events governing the inhibition of CFTR expression by various exogenous oxidative stress inducers remain unclear.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

NF-E2-related factor 2, a key inducer of antioxidant defenses, negatively regulates the CFTR transcription

René¹,

Lopez²,

Claustres³

et al. 2010

Cell. Mol. Life Sci.

View full text Add to dashboard Cite

A few studies have clearly indicated that oxidative stress suppresses the cystic fibrosis transmembrane conductance receptor (CFTR) function and expression. However, the mechanisms by which this occurs are still poorly understood. To clarify this effect, we investigated the role of NF-E2-related factor 2 (Nrf2) transcription factor, a key cellular sensor of oxidative stress. A conserved antioxidant response element (ARE) in the CFTR minimal promoter, which binds Nrf2, has been identified. Surprisingly, Nrf2 exerts an unexpected repressive role on the CFTR gene promoter activity. To decipher the molecular mechanisms involved, we evaluated the role of YY1 in the Nrf2-mediated transcriptional activity and showed cooperation between these two factors. We demonstrated that Nrf2 promotes YY1 nuclear localization and increases its binding to the CFTR promoter. To our knowledge, this study is the first to report a repressor role of Nrf2 through the cooperation with YY1 and contributes to clarify the cascade events leading to the oxidative stress-suppressed CFTR expression.

show abstract

Section: Discussionsupporting

confidence: 80%

Section: Introductionmentioning

confidence: 99%

NF-E2-related factor 2, a key inducer of antioxidant defenses, negatively regulates the CFTR transcription

René¹,

Lopez²,

Claustres³

et al. 2010

Cell. Mol. Life Sci.

View full text Add to dashboard Cite

show abstract

“…Rapid CFTR activation is also seen in the presence of the Pseudomonas aeruginosa virulence factor pyocyanin, likely via increased H 2 O 2 production (Schwarzer et al, 2008). It is noteworthy, however, that this initial stimulation by pyocyanin later gives way to an inhibition of CFTR activity, which is in line with other reports that longer-term exposure to oxidant stress can actually decrease CFTR activity and expression (Cantin et al, 2006;Schwarzer et al, 2008;Qu et al, 2009). Thus, there is a complex physiological response to oxidant stress, consisting of an acute stimulatory effect, followed by a suppression of CFTR activity.…”

Section: Introductionsupporting

confidence: 84%

The Prostaglandin E₂Type 4 Receptor Participates in the Response to Acute Oxidant Stress in Airway Epithelial Cells

Jones

Li²,

Cowley³

2012

J Pharmacol Exp Ther

View full text Add to dashboard Cite

Oxidative stress is implicated in the pathogenesis of many inflammatory pulmonary diseases, including cystic fibrosis (CF). Delineating how oxidative stress stimulates CF transmembrane conductance regulator (CFTR) in airway epithelial cells is useful, both to increase the understanding of airways host defense and suggest therapeutic approaches to reduce the oxidant stress burden in the CF lung. Using the airway epithelial cell line Calu-3, we investigated the hypothesis that hydrogen peroxide (H 2 O 2 ), which stimulates anion efflux through CFTR, does so via the production of prostaglandin E 2 (PGE 2 ). Using iodide efflux as a biochemical marker of CFTR activity and short circuit current (I sc ) recordings, we found that the H 2 O 2 -stimulated efflux was abolished by cyclooxygenase-1 inhibition and potentially also involves microsomal prostaglandin E synthase-1 activity, implicating a role for PGE 2 production. Furthermore, H 2 O 2 application resulted in a rapid release of PGE 2 from Calu-3 cells. We additionally hypothesized that the PGE 2 subtype 4 (EP 4 ) receptor was involved in mediating this response. In the presence of (4Z)-7-[(rel-1S,2S,5R)-5-((1,1Ј-biphenyl-4-yl)methoxy)-2-(4-morpholinyl)-3-oxocyclopentyl]-4-heptenoic acid (AH23848) (which blocks the EP 4 receptor), the H 2 O 2 -stimulated response was abolished. To investigate this finding in a polarized system, we measured the increase in I sc induced by H 2 O 2 addition in the presence and absence of AH23848. H 2 O 2 induced a robust increase in I sc , which was significantly attenuated in the presence of AH23848, suggesting some role for the EP 4 receptor. In conclusion, with H 2 O 2 as a model oxidant stress, stimulation of CFTR seems to involve PGE 2 production and likely EP 4 receptor activation in Calu-3 airway epithelial cells. This mechanism would be compromised in the CF airways.

show abstract

“…CFTR dysfunction-induced enhanced oxidative stress, decreased anti-inflammatory signaling and altered processing of IκB could result in increased cytokine production in CF cells [38], [49]. Ozone exposure by itself could cause downregulation of CFTR and decreased CFTR chloride current in human bronchial epithelial cells [50]. Further, a role of CFTR during the initiation of apoptosis in airway epithelial cells also has been proposed [51], [52].…”

Section: Discussionmentioning

confidence: 99%

SERCA2 Regulates Non-CF and CF Airway Epithelial Cell Response to Ozone

et al. 2011

View full text Add to dashboard Cite

Calcium mobilization can regulate a wide range of essential functions of respiratory epithelium, including ion transport, ciliary beat frequency, and secretion of mucus, all of which are modified in cystic fibrosis (CF). SERCA2, an important controller of calcium signaling, is deficient in CF epithelium. We conducted this study to determine whether SERCA2 deficiency can modulate airway epithelial responses to environmental oxidants such as ozone. This could contribute to the pathogenesis of pulmonary exacerbations, which are important and frequent clinical events in CF. To address this, we used air-liquid interface (ALI) cultures of non-CF and CF cell lines, as well as differentiated cultures of cells derived from non-CF and CF patients. We found that ozone exposure caused enhanced membrane damage, mitochondrial dysfunction and apoptotic cell death in CF airway epithelial cell lines relative to non-CF. Ozone exposure caused increased proinflammatory cytokine production in CF airway epithelial cell lines. Elevated proinflammatory cytokine production also was observed in shRNA-mediated SERCA2 knockdown cells. Overexpression of SERCA2 reversed ozone-induced proinflammatory cytokine production. Ozone-induced proinflammatory cytokine production was NF-κB- dependent. In a stable NF-κB reporter cell line, SERCA2 inhibition and knockdown both upregulated cytomix-induced NF-κB activity, indicating importance of SERCA2 in modulating NF-κB activity. In this system, increased NF-κB activity was also accompanied by increased IL-8 production. Ozone also induced NF-κB activity and IL-8 release, an effect that was greater in SERCA2-silenced NF-κB-reporter cells. SERCA2 overexpression reversed cytomix-induced increased IL-8 release and total nuclear p65 in CFTR-deficient (16HBE-AS) cells. These studies suggest that SERCA2 is an important regulator of the proinflammatory response of airway epithelial cells and could be a potential therapeutic target.

show abstract

Ozone stress down-regulates the expression of cystic fibrosis transmembrane conductance regulator in human bronchial epithelial cells

Cited by 36 publications

References 26 publications

NF-E2-related factor 2, a key inducer of antioxidant defenses, negatively regulates the CFTR transcription

NF-E2-related factor 2, a key inducer of antioxidant defenses, negatively regulates the CFTR transcription

The Prostaglandin E₂Type 4 Receptor Participates in the Response to Acute Oxidant Stress in Airway Epithelial Cells

SERCA2 Regulates Non-CF and CF Airway Epithelial Cell Response to Ozone

Contact Info

Product

Resources

About

Ozone stress down-regulates the expression of cystic fibrosis transmembrane conductance regulator in human bronchial epithelial cells

Cited by 36 publications

References 26 publications

NF-E2-related factor 2, a key inducer of antioxidant defenses, negatively regulates the CFTR transcription

NF-E2-related factor 2, a key inducer of antioxidant defenses, negatively regulates the CFTR transcription

The Prostaglandin E2Type 4 Receptor Participates in the Response to Acute Oxidant Stress in Airway Epithelial Cells

SERCA2 Regulates Non-CF and CF Airway Epithelial Cell Response to Ozone

Contact Info

Product

Resources

About

The Prostaglandin E₂Type 4 Receptor Participates in the Response to Acute Oxidant Stress in Airway Epithelial Cells