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

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.

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

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.00110.2004 ◽

2004 ◽

Vol 287 (4) ◽

pp. L774-L783 ◽

Cited By ~ 211

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.

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Eosinophil Responses at the Airway Epithelial Barrier during the Early Phase of Influenza a Virus Infection in C57BL/6 Mice

Cells ◽

10.3390/cells10030509 ◽

2021 ◽

Vol 10 (3) ◽

pp. 509 ◽

Cited By ~ 1

Author(s):

Meenakshi Tiwary ◽

Robert J. Rooney ◽

Swantje Liedmann ◽

Kim S. LeMessurier ◽

Amali E. Samarasinghe

Keyword(s):

Epithelial Cells ◽

Influenza A Virus ◽

Early Phase ◽

Influenza A ◽

Airway Epithelial Cells ◽

Epithelial Barrier ◽

Virus Infectivity ◽

Airway Epithelial ◽

In Vivo Models

Eosinophils, previously considered terminally differentiated effector cells, have multifaceted functions in tissues. We previously found that allergic mice with eosinophil-rich inflammation were protected from severe influenza and discovered specialized antiviral effector functions for eosinophils including promoting cellular immunity during influenza. In this study, we hypothesized that eosinophil responses during the early phase of influenza contribute to host protection. Using in vitro and in vivo models, we found that eosinophils were rapidly and dynamically regulated upon influenza A virus (IAV) exposure to gain migratory capabilities to traffic to lymphoid organs after pulmonary infection. Eosinophils were capable of neutralizing virus upon contact and combinations of eosinophil granule proteins reduced virus infectivity through hemagglutinin inactivation. Bi-directional crosstalk between IAV-exposed epithelial cells and eosinophils occurred after IAV infection and cross-regulation promoted barrier responses to improve antiviral defenses in airway epithelial cells. Direct interactions between eosinophils and airway epithelial cells after IAV infection prevented virus-induced cytopathology in airway epithelial cells in vitro, and eosinophil recipient IAV-infected mice also maintained normal airway epithelial cell morphology. Our data suggest that eosinophils are important in the early phase of IAV infection providing immediate protection to the epithelial barrier until adaptive immune responses are deployed during influenza.

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Infection of bovine well-differentiated airway epithelial cells by Pasteurella multocida: actions and counteractions in the bacteria–host interactions

Veterinary Research ◽

10.1186/s13567-020-00861-2 ◽

2020 ◽

Vol 51 (1) ◽

Author(s):

Ang Su ◽

Jie Tong ◽

Yuguang Fu ◽

Sandy Müller ◽

Yenehiwot Berhanu Weldearegay ◽

...

Keyword(s):

Epithelial Cell ◽

Epithelial Cells ◽

Cell Layer ◽

Airway Epithelial Cells ◽

Infection Model ◽

Target Cells ◽

Respiratory Disorder ◽

Airway Epithelial ◽

Epithelial Cell Layer ◽

Well Differentiated

AbstractPasteurella (P.) multocida is a zoonotic pathogen, which is able to cause respiratory disorder in different hosts. In cattle, P. multocida is an important microorganism involved in the bovine respiratory disease complex (BRDC) with a huge economic impact. We applied air–liquid interface (ALI) cultures of well-differentiated bovine airway epithelial cells to analyze the interaction of P. multocida with its host target cells. The bacterial pathogen grew readily on the ALI cultures. Infection resulted in a substantial loss of ciliated cells. Nevertheless, the epithelial cell layer maintained its barrier function as indicated by the transepithelial electrical resistance and the inability of dextran to get from the apical to the basolateral compartment via the paracellular route. Analysis by confocal immunofluorescence microscopy confirmed the intactness of the epithelial cell layer though it was not as thick as the uninfected control cells. Finally, we chose the bacterial neuraminidase to show that our infection model is a sustainable tool to analyze virulence factors of P. multocida. Furthermore, we provide an explanation, why this microorganism usually is a commensal and becomes pathogenic only in combination with other factors such as co-infecting microorganisms.

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

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.1997.272.5.l888 ◽

1997 ◽

Vol 272 (5) ◽

pp. L888-L896 ◽

Cited By ~ 26

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.

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Olodaterol and anti-inflammatory effects on differentiated air-liquid interface cultures of airway epithelial cells

10.1183/1393003.congress-2017.pa1000 ◽

2017 ◽

Author(s):

Gurpreet Singhera ◽

Roxana Yan ◽

Delbert Dorscheid ◽

Don Sin ◽

Michael Pieper

Keyword(s):

Epithelial Cells ◽

Airway Epithelial Cells ◽

Liquid Interface ◽

Airway Epithelial ◽

Anti Inflammatory ◽

Air Liquid Interface

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

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.00025.2004 ◽

2004 ◽

Vol 287 (1) ◽

pp. L94-L103 ◽

Cited By ~ 89

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.

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Airway epithelial cells modify immune responses by inducing an anti-inflammatory microenvironment

European Journal of Immunology ◽

10.1002/eji.200737936 ◽

2008 ◽

Vol 38 (6) ◽

pp. 1689-1699 ◽

Cited By ~ 70

Author(s):

Anja K. Mayer ◽

Holger Bartz ◽

Fabian Fey ◽

Lotte M. Schmidt ◽

Alexander H. Dalpke

Keyword(s):

Epithelial Cells ◽

Immune Responses ◽

Airway Epithelial Cells ◽

Airway Epithelial ◽

Inflammatory Microenvironment ◽

Anti Inflammatory

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Methoxyphenols Exhibit Anti-inflammatory Effects on Airway Epithelial Cells by Acting Post-transcriptionally

Journal of Allergy and Clinical Immunology ◽

10.1016/j.jaci.2011.12.424 ◽

2012 ◽

Vol 129 (2) ◽

pp. AB127

Author(s):

F.T. Ishmael ◽

K.R. Houser ◽

D. Johnson

Keyword(s):

Epithelial Cells ◽

Airway Epithelial Cells ◽

Airway Epithelial ◽

Anti Inflammatory

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

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.00483.2001 ◽

2002 ◽

Vol 283 (3) ◽

pp. L612-L618 ◽

Cited By ~ 26

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.

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