Asian Sand Dust Regulates IL-32 Production in Airway Epithelial Cells: Inhibitory Effect of Glucocorticoids

2019 ◽  
Vol 33 (4) ◽  
pp. 403-412 ◽  
Author(s):  
Jae-Min Shin ◽  
Hwee-Jin Kim ◽  
Joo-Hoo Park ◽  
You Jin Hwang ◽  
Heung-Man Lee
Keyword(s):  
Epithelial Cells ◽  
Signaling Pathways ◽  
Ex Vivo ◽  
A549 Cells ◽  
Inhibitory Effect ◽  
Airway Epithelial Cells ◽  
Airway Epithelial ◽  
Organ Cultures ◽  
Nasal Epithelial Cells ◽  
Asian Sand Dust

Purpose Epidemiologic studies have reported that Asian sand dust (ASD) is associated with chronic inflammatory diseases of the respiratory system. Glucocorticoids (GCs) have potent anti-inflammatory properties. The aims of this study were to evaluate the effects of GCs on ASD-induced interleukin-32 (IL-32) expression and to identify the underlying signaling pathways in airway epithelial cells. Methods A 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay was used to evaluate cytotoxicity in A549 and human primary nasal epithelial cells. Expression levels of IL-32 messenger RNA and protein were measured by Western blot, real-time polymerase chain reaction, ELISA, and immunofluorescence staining. Signaling pathways were analyzed using specific inhibitors of Akt, MAPK, or NF- κB. The effects of GCs on the expression of ASD-induced IL-32 were confirmed with ex vivo organ cultures of the nasal interior turbinate. Results ASD (0–400 ng/mL) had no significant cytotoxic effects in A549 cells and human primary nasal epithelial cells. Expression levels of IL-32 were dose-dependently upregulated by ASD treatment in A549 cells. ASD induced phosphorylation of Akt, MAPK, and NF-κB, whereas GCs and specific inhibitors of Akt, MAPK, and NF-κB downregulated these activations and the expression of IL-32. These findings were further confirmed in human primary nasal epithelial cells and ex vivo organ cultures of the nasal interior turbinate. Conclusions GCs have an inhibitory effect on ASD-induced IL-32 expression via the Akt, MAPK, and NF- κB signaling pathways in airway epithelial cells.

scholarly journals Incomplete Regulation of NF-κB by IκBα during Respiratory Syncytial Virus Infection in A549 Cells

1999 ◽  
Vol 73 (5) ◽  
pp. 4502-4507 ◽  
Author(s):  
Michael A. Fiedler ◽  
Kara Wernke-Dollries
Keyword(s):  
Respiratory Syncytial Virus ◽  
Epithelial Cells ◽  
A549 Cells ◽  
Inhibitory Effect ◽  
Airway Epithelial Cells ◽  
Airway Epithelial ◽  
Necrosis Factor Alpha ◽  
Tnf Α ◽  
Rsv Infection ◽  
Syncytial Virus

ABSTRACT Respiratory syncytial virus (RSV) infection of airway epithelial cells results in persistent NF-κB activation and NF-κB-mediated interleukin-8 production. Previous studies in airway epithelial cells demonstrated that tumor necrosis factor alpha (TNF-α)-induced NF-κB activation is transient due to regulation by IκBα. However, during RSV infection, IκBα has only a partial inhibitory effect on NF-κB activation. Studies presented here demonstrate that neither increased IκBα production which occurs as a result of RSV-induced NF-κB activation nor inhibition of proteasome-mediated IκBα degradation results in a reversal of RSV-induced NF-κB activation. Thus, while manipulation of IκBα results in reversal of TNF-α-induced NF-κB activation, manipulation of IκBα does not result in a reversal of RSV-induced NF-κB activation.

scholarly journals Anti-Inflammatory Properties of Fructo-Oligosaccharides in a Calf Lung Infection Model and in Mannheimia haemolytica-Infected Airway Epithelial Cells

Nutrients ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 3514
Author(s):  
Yang Cai ◽  
Myrthe S. Gilbert ◽  
Walter J. J. Gerrits ◽  
Gert Folkerts ◽  
Saskia Braber
Keyword(s):  
Epithelial Cells ◽  
A549 Cells ◽  
Airway Epithelial Cells ◽  
Mannheimia Haemolytica ◽  
Epithelial Barrier ◽  
Infection Model ◽  
Airway Epithelial ◽  
Clinical Scores ◽  
Lung Infections ◽  
Anti Inflammatory

Emerging antimicrobial-resistant pathogens highlight the importance of developing novel interventions. Here, we investigated the anti-inflammatory properties of Fructo-oligosaccharides (FOS) in calf lung infections and in airway epithelial cells stimulated with pathogens, and/or bacterial components. During a natural exposure, 100 male calves were fed milk replacer with or without FOS for 8 weeks. Then, immune parameters and cytokine/chemokine levels in the bronchoalveolar lavage fluid (BALF) and blood were measured, and clinical scores were investigated. Calf primary bronchial epithelial cells (PBECs) and human airway epithelial cells (A549) were treated with Mannheimia haemolytica, lipopolysaccharides (LPS), and/or flagellin, with or without FOS pretreatment. Thereafter, the cytokine/chemokine levels and epithelial barrier function were examined. Relative to the control (naturally occurring lung infections), FOS-fed calves had greater macrophage numbers in BALF and lower interleukin (IL)-8, IL-6, and IL-1β concentrations in the BALF and blood. However, FOS did not affect the clinical scores. At slaughter, FOS-fed calves had a lower severity of lung lesions compared to the control. Ex vivo, FOS prevented M. haemolytica-induced epithelial barrier dysfunction. Moreover, FOS reduced M. haemolytica- and flagellin-induced (but not LPS-induced) IL-8, TNF-α, and IL-6 release in PBECs and A549 cells. Overall, FOS had anti-inflammatory properties during the natural incidence of lung infections but had no effects on clinical symptoms.

scholarly journals Mechanical stretch decreases FAK phosphorylation and reduces cell migration through loss of JIP3-induced JNK phosphorylation in airway epithelial cells

2009 ◽  
Vol 297 (3) ◽  
pp. L520-L529 ◽  
Author(s):  
Leena P. Desai ◽  
Steven R. White ◽  
Christopher M. Waters
Keyword(s):  
Cell Migration ◽  
Epithelial Cells ◽  
Mechanical Strain ◽  
Mechanical Stretch ◽  
Inhibitory Effect ◽  
Airway Epithelial Cells ◽  
Airway Epithelial ◽  
Interacting Protein ◽  
Kinase Activation ◽  
Mapk Cascades

JNK is a nonreceptor kinase involved in the early events that signal cell migration after injury. However, the linkage to early signals required to initiate the migration response to JNK has not been defined in airway epithelial cells, which exist in an environment subjected to cyclic mechanical strain (MS). The present studies demonstrate that the JNK/stress-activated protein kinase-associated protein 1 (JSAP1; also termed JNK-interacting protein 3, JIP3), a scaffold factor for MAPK cascades that links JNK activation to focal adhesion kinase (FAK), are both associated and activated following mechanical injury in 16HBE14o− human airway epithelial cells and that both FAK and JIP3 phosphorylation seen after injury are decreased in cells subjected to cyclic MS. Overexpression of either wild-type (WT)-FAK or WT-JIP3 enhanced phosphorylation and kinase activation of JNK and reduced the inhibitory effect of cyclic MS. These results suggest that cyclic MS impairs signaling of cell migration after injury via a pathway that involves FAK-JIP3-JNK.

Alpha 1-adrenergic signaling in human airway epithelial cells involves inositol lipid and phosphate metabolism

1992 ◽  
Vol 262 (2) ◽  
pp. L183-L191 ◽  
Author(s):  
C. M. Liedtke
Keyword(s):  
Epithelial Cells ◽  
Inositol Phosphates ◽  
Inositol Phosphate ◽  
Airway Epithelial Cells ◽  
Airway Epithelial ◽  
Nasal Epithelial Cells ◽  
Human Airway ◽  
Adrenergic Antagonist ◽  
Human Airway Epithelial Cells

A role for phospholipase C (PLC) hydrolysis of phosphatidylinositol 4,5-bisphosphate (PIP2) as a mechanism of alpha 1-adrenergic signal transduction in human airway epithelial cells (AEC) was investigated in isolated normal tracheal and cystic fibrosis (CF) nasal epithelial cells grown in in vitro culture and prelabeled with 3 muCi myo-[3H]inositol/ml for 72 h. Breakdown of polyphosphoinositides was measured using thin-layer chromatography to detect phosphatidylinositol, phosphatidylinositol 4-phosphate (PIP), and PIP2. Inositol phosphates were separated by ion-exchange column chromatography. In normal AEC, the addition of the endogenous catecholamine l-epinephrine produced a rapid, transient accumulation of inositol 1,4,5-trisphosphate (IP3) and inositol 1,4-bisphosphate (IP2) and breakdown of PIP and PIP2. IP3 increased 1.7-fold and IP2 1.6-fold after 20 and 40 s, respectively. A maximal decrease of 35% PIP2 and 30% PIP is observed after 20 and 40 s, respectively. The effects of l-epinephrine were not blocked by the beta-adrenergic antagonist dl-propranolol but were mimicked by the alpha 1-adrenergic agonist methoxamine. Prazosin, an alpha 1-adrenergic antagonist, and pertussis toxin (PTX) blocked the effects of l-epinephrine and methoxamine. Addition of l-epinephrine and methoxamine to CF nasal epithelial cells also induced prazosin-sensitive polyphosphoinositide breakdown and inositol phosphate accumulation. A 2.2-fold accumulation of IP3 was observed after 10 s and 2.0-fold increase in IP2 after 20 s. Maximal decreases of 32% PIP2 and 23% PIP levels were observed after 20-s incubation with l-epinephrine. PTX reduced the effects of l-epinephrine and significantly blocked the effects of methoxamine.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of defensins on interleukin-8 synthesis in airway epithelial cells

1997 ◽  
Vol 272 (5) ◽  
pp. L888-L896 ◽  
Author(s):  
S. Van Wetering ◽  
S. P. Mannesse-Lazeroms ◽  
M. A. Van Sterkenburg ◽  
M. R. Daha ◽  
J. H. Dijkman ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Neutrophil Elastase ◽  
Proteinase Inhibitor ◽  
De Novo ◽  
Tissue Injury ◽  
A549 Cells ◽  
Airway Epithelial Cells ◽  
Epithelial Cell Line ◽  
Mrna Levels ◽  
Airway Epithelial

Neutrophils play an important role in inflammatory processes in the lung and may cause tissue injury through, for example, release of proteinases such as neutrophil elastase. In addition to neutrophil elastase, stimulated neutrophils also release small nonenzymatic and cationic polypeptides termed defensins. The aim of the present study was to investigate whether defensins induce interleukin (IL)-8 expression in cells of the A549 lung epithelial cell line and in human primary bronchial epithelial cells (PBEC). Supernatants of defensin-treated A549 cells contained increased neutrophil chemotactic activity (16-fold) that was inhibited by antibodies against IL-8. Concurrently, within 3 and 6 h, defensins significantly increased the IL-8 levels in supernatants of both A549 cells (n = 6, P < 0.05 and P < 0.01, respectively) and PBEC (n = 4, P < 0.001 and P < 0.001, respectively). This defensin-induced increase was fully inhibited by the serine proteinase inhibitor alpha 1-proteinase inhibitor. In addition, defensins also increased IL-8 mRNA levels (12-fold); this increase was dependent on de novo mRNA synthesis and did not require protein synthesis. Furthermore, defensins did not affect IL-8 mRNA stability, indicating that the enhanced IL-8 expression was due to increased transcription. Our findings suggest that defensins, released by stimulated neutrophils, stimulate IL-8 synthesis by airway epithelial cells and thus may mediate the recruitment of additional neutrophils into the airways.

Pseudomonas aeruginosapyocyanin directly oxidizes glutathione and decreases its levels in airway epithelial cells

2004 ◽  
Vol 287 (1) ◽  
pp. L94-L103 ◽  
Author(s):  
Yunxia Q. O'Malley ◽  
Krzysztof J. Reszka ◽  
Douglas R. Spitz ◽  
Gerene M. Denning ◽  
Bradley E. Britigan
Keyword(s):  
Epithelial Cell ◽  
Epithelial Cells ◽  
Culture Media ◽  
Alveolar Epithelial Cell ◽  
A549 Cells ◽  
Airway Epithelial Cells ◽  
Airway Epithelial ◽  
Alternative Source ◽  
Cell Functions

Production of pyocyanin enhances Pseudomonas aeruginosa virulence. Many of pyocyanin's in vitro and in vivo cytotoxic effects on human cells appear to result from its ability to redox cycle. Pyocyanin directly accepts electrons from NADH or NADPH with subsequent electron transfer to oxygen, generating reactive oxygen species. Reduced glutathione (GSH) is an important cellular antioxidant, and it contributes to the regulation of redox-sensitive signaling systems. Using the human bronchial epithelial (HBE) and the A549 human type II alveolar epithelial cell lines, we tested the hypothesis that pyocyanin can deplete airway epithelial cells of GSH. Incubation of both cell types with pyocyanin led to a concentration-dependent loss of cellular GSH (up to 50%) and an increase in oxidized GSH (GSSG) in the HBE, but not A549 cells, at 24 h. An increase in total GSH, mostly as GSSG, was detected in the culture media, suggesting export of GSH or GSSG from the pyocyanin-exposed cells. Loss of GSH could be due to pyocyanin-induced H2O2formation. However, overexpression of catalase only partially prevented the pyocyanin-mediated decline in cellular GSH. Cell-free electron paramagnetic resonance studies revealed that pyocyanin directly oxidizes GSH, forming pyocyanin free radical and O2−·. Pyocyanin oxidized other thiol-containing compounds, cysteine and N-acetyl-cysteine, but not methionine. Thus GSH may enhance pyocyanin-induced cytotoxicity by functioning as an alternative source of reducing equivalents for pyocyanin redox cycling. Pyocyanin-mediated alterations in cellular GSH may alter epithelial cell functions by modulating redox sensitive signaling events.

Anti-inflammatory effects of resveratrol in lung epithelial cells: molecular mechanisms

2004 ◽  
Vol 287 (4) ◽  
pp. L774-L783 ◽  
Author(s):  
Louise E. Donnelly ◽  
Robert Newton ◽  
Gina E. Kennedy ◽  
Peter S. Fenwick ◽  
Rachel H. F. Leung ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
A549 Cells ◽  
Airway Epithelial Cells ◽  
Airway Epithelial ◽  
Colony Stimulating Factor ◽  
Macrophage Colony Stimulating Factor ◽  
Anti Inflammatory ◽  
Macrophage Colony ◽  
Stimulating Factor ◽  
Factor Release

Resveratrol (3,4′,5-trihydroxystilbene) is a polyphenolic stilbene found in the skins of red fruits, including grapes, that may be responsible for some of the health benefits ascribed to consumption of red wine. Resveratrol has been shown to have antioxidant properties and can act as an estrogen agonist. This study examined the anti-inflammatory effects of resveratrol on human airway epithelial cells. Resveratrol and the related molecule quercetin, but not deoxyrhapontin, inhibited IL-8 and granulocyte-macrophage colony-stimulating factor release from A549 cells. Neither the estrogen receptor antagonist tamoxifen nor the glucocorticoid antagonist mifepristone altered the inhibitory effect of resveratrol. The mechanism of resveratrol action was investigated further using luciferase reporter genes stably transfected into A549 cells. Resveratrol and quercetin inhibited NF-κB-, activator protein-1-, and cAMP response element binding protein-dependent transcription to a greater extent than the glucocorticosteroid dexamethasone. These compounds also had no significant effect on acetylation or deacetylation of core histones. Resveratrol, but not estradiol or N-acetyl cysteine, inhibited cytokine-stimulated inducible nitric oxide synthase expression and nitrite production (IC50 = 3.6 ± 2.9 μM) in human primary airway epithelial cells. Resveratrol also inhibited granulocyte-macrophage colony-stimulating factor release (IC50 = 0.44 ± 0.17 μM), IL-8 release (IC50 = 4.7 ± 3.3 μM), and cyclooxygenase-2 expression in these cells. This study demonstrates that resveratrol and quercetin have novel nonsteroidal anti-inflammatory activity that may have applications for the treatment of inflammatory diseases.

scholarly journals Ciliary Beating Recovery in Deficient Human Airway Epithelial Cells after Lentivirus Ex Vivo Gene Therapy

PLoS Genetics ◽  
2009 ◽  
Vol 5 (3) ◽  
pp. e1000422 ◽  
Author(s):  
Brigitte Chhin ◽  
Didier Negre ◽  
Olivier Merrot ◽  
Jacqueline Pham ◽  
Yves Tourneur ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Epithelial Cells ◽  
Ex Vivo ◽  
Airway Epithelial Cells ◽  
Airway Epithelial ◽  
Ciliary Beating ◽  
Human Airway ◽  
Ex Vivo Gene Therapy ◽  
Human Airway Epithelial Cells

Bradykinin increases IL-8 generation in airway epithelial cells via COX-2-derived prostanoids

2002 ◽  
Vol 283 (3) ◽  
pp. L612-L618 ◽  
Author(s):  
Helen C. Rodgers ◽  
Linhua Pang ◽  
Elaine Holland ◽  
Lisa Corbett ◽  
Simon Range ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Epithelial Cells ◽  
A549 Cells ◽  
Airway Epithelial Cells ◽  
Prostaglandin E ◽  
Airway Epithelial ◽  
Neutrophilic Inflammation ◽  
Airway Diseases ◽  
Cox Inhibitor ◽  
Cox 2

Interleukin (IL)-8, the C-X-C chemokine, is a potent neutrophil chemoattractant that has been implicated in a number of inflammatory airway diseases such as cystic fibrosis. Here we tested the hypothesis that bradykinin, an inflammatory mediator and chloride secretagogue, would increase IL-8 generation in airway epithelial cells through autocrine generation of endogenous prostanoids. Bradykinin increased IL-8 generation in both a non-cystic fibrosis (A549) and cystic fibrosis epithelial cell line (CFTE29[Formula: see text]) that was inhibited by the nonselective cyclooxygenase (COX) inhibitor indomethacin and the COX-2 selective inhibitor NS-398. COX-2 was the only isoform of COX expressed in both cell lines. Furthermore, the COX substrate arachidonic acid and exogenous prostaglandin E2 both increased IL-8 release in A549 cells. These results suggest that bradykinin may contribute to neutrophilic inflammation in the airway by generation of IL-8 from airway epithelial cells. The dependence of this response on endogenous production of prostanoids by COX-2 suggests that selective COX-2 inhibitors may have a role in the treatment of airway diseases characterized by neutrophilic inflammation such as cystic fibrosis or chronic obstructive pulmonary disease.

Sign in / Sign up

Export Citation Format

Share Document