Fluticasone propionate and Salmeterol combination induces SOCS-3 expression in airway epithelial cells

Nasreen, Najmunnisa; Khodayari, Nazli; Sukka-Ganesh, Bhagyalaxmi; Pothapregada, Sriram; Mohammed, Kamal A.

doi:10.1016/j.intimp.2011.11.014

Cited by 10 publications

(16 citation statements)

References 48 publications

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“…Some cultures were transfected with siRNA-EphA2 or control-siRNA prior to TS exposure. BAEpCs were exposed to varying concentrations of TS, i.e., 1 exposure unit (EU), 2EU, 3EU, or 4EU, as reported earlier (32). Briefly, the 1EU of TS consists of 15 min of TS exposure followed by 45 min of incubation in 5% CO2 and 95% ambient air.…”

Section: Methodsmentioning

confidence: 99%

“…BAEpCs cultured in 60-mm culture dishes (Corning, Tewksbury, MA) were exposed to varying concentration of TS, and the expression of EphA2 and EphrinA1 was detected using rabbit anti-human EphA2 and rabbit anti-human EphrinA1, respectively. Some BAEpC cultures were exposed to TS either in the presence of MAPK inhibitors or siRNA-EphA2, and focal adhesion proteins paxillin and E-cadherin were detected using rabbit antihuman paxillin, and rabbit anti-human E-cadherin (BD Transduction Labs, Franklin Lakes, NJ), respectively, as reported earlier (32,33). In brief, cells were lysed in radioimmunoprecipitation assay (RIPA) buffer 50 mM Tris-HCl, pH 8.0, with 150 mM sodium chloride, 0.5% sodium deoxycholate, and 0.1% sodium dodecyl sulfate.…”

Section: Methodsmentioning

confidence: 99%

“…After 10, 15, and 20 h of TS exposure, significant decreases in resistance were observed compared with control (room air exposed) BAEpCs. In a recent study we reported that TS (1EU-4EU) exposure induced the phosphorylation of Erk1/Erk2 and p38 MAPK in BAEpCs in a concentration-dependent manner (32). To determine the potential role of MAPKs in TS-induced decrease in cellular resistance, we pretreated the BAEpC monolayers with pharmacological inhibitors to Erk1/2, p38, and JNK and exposed them to TS or room air and measured the resistance over time.…”

Section: Ts Upregulated Epha2 Receptor and Its Ligand Ephrina1 Expresmentioning

confidence: 99%

“…Activation of these signaling cascades leads to translocation of nuclear factors, such as NF-kB, to the nucleus, which in turn affects the expression of target gene or phosphorylation of transcription factors in the nucleus (47). In a recent study, we reported that TS exposure activates MAPK in BAEpCs (32). However, whether these activated MAPK in TS-exposed BAEpCs play a role in the modulation of airway epithelial E-cadherin expression and the permeability have not been investigated.…”

mentioning

confidence: 97%

“…Cellular response to external stimuli, such as TS, is controlled by a complex array of mitogen-activated protein kinase (MAPK) signaling pathways (8,27,32). The MAPK are an important group of serine/threonine signaling kinases that play a key role in converting stress stimuli into nuclear responses.…”

mentioning

confidence: 99%

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Tobacco smoke induces epithelial barrier dysfunction via receptor EphA2 signaling

Nasreen

Khodayari

Pothapregada

et al. 2014

American Journal of Physiology-Cell Physiology

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Erythropoietin-producing human hepatocellular carcinoma (Eph) receptors are the largest family of receptor tyrosine kinases (RTKs) that mediate various cellular and developmental processes. The degrees of expression of these key molecules control the cell-cell interactions. Although the role of Eph receptors and their ligand Ephrins is well studied in developmental processes, their function in tobacco smoke (TS)-induced epithelial barrier dysfunction is unknown. We hypothesized that TS may induce permeability in bronchial airway epithelial cell (BAEpC) monolayer by modulating receptor EphA2 expression, actin cytoskeleton, adherens junction, and focal adhesion proteins. Here we report that in BAEpCs, acute TS exposure significantly upregulated EphA2 and EphrinA1 expression, disrupted the actin filaments, decreased E-cadherin expression, and increased protein permeability, whereas the focal adhesion protein paxillin was unaffected. Silencing the receptor EphA2 expression with silencing interference RNA (siRNA) significantly attenuated TS-induced hyperpermeability in BAEpCs. In addition, when BAEpC monolayer was transfected with EphA2-expressing plasmid and treated with recombinant EphrinA1, the transepithelial electrical resistance decreased significantly. Furthermore, TS downregulated E-cadherin expression and induced hyperpermeability across BAEpC monolayer in a Erk1/Erk2, p38, and JNK MAPK-dependent manner. TS induced hyperpermeability in BAEpC monolayer by targeting cell-cell adhesions, and interestingly cell-matrix adhesions were unaffected. The present data suggest that TS causes significant damage to the BAEpCs via induction of EphA2 and downregulation of E-cadherin. Induction of EphA2 in the BAEpCs exposed to TS may be an important signaling event in the pathogenesis of TS-induced epithelial injury.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Ts Upregulated Epha2 Receptor and Its Ligand Ephrina1 Expresmentioning

confidence: 99%

mentioning

confidence: 97%

mentioning

confidence: 99%

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Tobacco smoke induces epithelial barrier dysfunction via receptor EphA2 signaling

Nasreen

Khodayari

Pothapregada

et al. 2014

American Journal of Physiology-Cell Physiology

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A novel chi‐square statistic for detecting group differences between pathways in systems epidemiology

Yuan

Zhang

et al. 2016

Statistics in Medicine

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Traditional epidemiology often pays more attention to the identification of a single factor rather than to the pathway that is related to a disease, and therefore, it is difficult to explore the disease mechanism. Systems epidemiology aims to integrate putative lifestyle exposures and biomarkers extracted from multiple omics platforms to offer new insights into the pathway mechanisms that underlie disease at the human population level. One key but inadequately addressed question is how to develop powerful statistics to identify whether one candidate pathway is associated with a disease. Bearing in mind that a pathway difference can result from not only changes in the nodes but also changes in the edges, we propose a novel statistic for detecting group differences between pathways, which in principle, captures the nodes changes and edge changes, as well as simultaneously accounting for the pathway structure simultaneously. The proposed test has been proven to follow the chi-square distribution, and various simulations have shown it has better performance than other existing methods. Integrating genome-wide DNA methylation data, we analyzed one real data set from the Bogalusa cohort study and significantly identified a potential pathway, Smoking → SOCS3 → PIK3R1, which was strongly associated with abdominal obesity. The proposed test was powerful and efficient at identifying pathway differences between two groups, and it can be extended to other disciplines that involve statistical comparisons between pathways. The source code in R is available on our website. Copyright © 2016 John Wiley & Sons, Ltd.

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How Phosphodiesterase 4 Inhibitors Work in Patients with Chronic Obstructive Pulmonary Disease of the Severe, Bronchitic, Frequent Exacerbator Phenotype

Giembycz

Newton

2014

Clinics in Chest Medicine

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Fluticasone propionate and Salmeterol combination induces SOCS-3 expression in airway epithelial cells

Cited by 10 publications

References 48 publications

Tobacco smoke induces epithelial barrier dysfunction via receptor EphA2 signaling

Tobacco smoke induces epithelial barrier dysfunction via receptor EphA2 signaling

A novel chi‐square statistic for detecting group differences between pathways in systems epidemiology

How Phosphodiesterase 4 Inhibitors Work in Patients with Chronic Obstructive Pulmonary Disease of the Severe, Bronchitic, Frequent Exacerbator Phenotype

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