The Role Of Respiratory Epithelial Cells In The Pathophysiological Function Of PPAR-gamma

GATA-6, a member of a family of zinc finger transcription factors, is expressed in epithelial cells of the developing lung. To further assess the role of GATA-6 in lung morphogenesis, GATA-6 was expressed in respiratory epithelial cells of the developing mouse lung under control of the surfactant protein C promoter (hSP-CGATA-6 mice). Although GATA-6 did not alter lung morphology at embryonic day 18.5, defects in alveolar septation were observed early in the neonatal period, and air space enlargement persisted to adulthood. Airway resistance, airway elastance, tissue damping, and tissue elastance were significantly decreased, and lung volumes were significantly increased at 12 wk of age. Normal postnatal morphogenesis of the lung depends upon precise temporal-spatial regulation of GATA-6.

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A Role of Epithelial Cells and Virulence Factors in Biofilm Formation by Streptococcus pyogenes In Vitro

Infection and Immunity ◽

10.1128/iai.00133-20 ◽

2020 ◽

Vol 88 (10) ◽

Author(s):

Feiruz Alamiri ◽

Yashuan Chao ◽

Maria Baumgarten ◽

Kristian Riesbeck ◽

Anders P. Hakansson

Keyword(s):

Antibiotic Resistance ◽

Epithelial Cells ◽

Virulence Factors ◽

Streptococcus Pyogenes ◽

Biofilm Formation ◽

Model Systems ◽

Respiratory Epithelial Cells ◽

Abiotic Surfaces ◽

Respiratory Epithelial

ABSTRACT Biofilm formation by Streptococcus pyogenes (group A streptococcus [GAS]) in model systems mimicking the respiratory tract is poorly documented. Most studies have been conducted on abiotic surfaces, which poorly represent human tissues. We have previously shown that GAS forms mature and antibiotic-resistant biofilms on physiologically relevant epithelial cells. However, the roles of the substratum, extracellular matrix (ECM) components, and GAS virulence factors in biofilm formation and structure are unclear. In this study, biofilm formation was measured on respiratory epithelial cells and keratinocytes by determining biomass and antibiotic resistance, and biofilm morphology was visualized using scanning electron microscopy. All GAS isolates tested formed biofilms that had similar, albeit not identical, biomass and antibiotic resistance for both cell types. Interestingly, functionally mature biofilms formed more rapidly on keratinocytes but were structurally denser and coated with more ECM on respiratory epithelial cells. The ECM was crucial for biofilm integrity, as protein- and DNA-degrading enzymes induced bacterial release from biofilms. Abiotic surfaces supported biofilm formation, but these biofilms were structurally less dense and organized. No major role for M protein, capsule, or streptolysin O was observed in biofilm formation on epithelial cells, although some morphological differences were detected. NAD-glycohydrolase was required for optimal biofilm formation, whereas streptolysin S and cysteine protease SpeB impaired this process. Finally, no correlation was found between cell adherence or autoaggregation and GAS biofilm formation. Combined, these results provide a better understanding of the role of biofilm formation in GAS pathogenesis and can potentially provide novel targets for future treatments against GAS infections.

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Role of Pht Proteins in Attachment of Streptococcus pneumoniae to Respiratory Epithelial Cells

Infection and Immunity ◽

10.1128/iai.00699-13 ◽

2014 ◽

Vol 82 (4) ◽

pp. 1683-1691 ◽

Cited By ~ 30

Author(s):

Anna Kallio ◽

Kirsi Sepponen ◽

Philippe Hermand ◽

Philippe Denoël ◽

Fabrice Godfroid ◽

...

Keyword(s):

Epithelial Cells ◽

Bacterial Attachment ◽

Surface Proteins ◽

Lung Epithelial Cells ◽

Host Cells ◽

Respiratory Epithelial Cells ◽

Relative Significance ◽

Mucosal Surfaces ◽

Respiratory Epithelial

ABSTRACTPneumococcal adherence to mucosal surfaces is a critical step in nasopharyngeal colonization, but so far few pneumococcal adhesins involved in the interaction with host cells have been identified. PhtA, PhtB, PhtD, and PhtE are conserved pneumococcal surface proteins that have proven promising as vaccine candidates. One suggested virulence function of Pht proteins is to mediate adherence at the respiratory mucosa. In this study, we assessed the role of Pht proteins in pneumococcal binding to respiratory epithelial cells. Pneumococci were incubated with human nasopharyngeal epithelial cells (Detroit-562) and lung epithelial cells (A549 and NCI-H292), and the proportion of bound bacteria was measured by plating viable counts. Strains R36A (unencapsulated), D39 (serotype 2), 43 (serotype 3), 4-CDC (serotype 4), and 2737 (serotype 19F) with one or more of the four homologous Pht proteins deleted were compared with their wild-type counterparts. Also, the effect of anti-PhtD antibodies on the adherence of strain 2737 to the respiratory epithelial cells was studied. Our results suggest that Pht proteins play a role in pneumococcal adhesion to the respiratory epithelium. We also found that antibody to PhtD is able to inhibit bacterial attachment to the cells, suggesting that antibodies against PhtD present at mucosal surfaces might protect from pneumococcal attachment and subsequent colonization. However, the relative significance of Pht proteins to the ability of pneumococci to bindin vitroto epithelial cells depends on the genetic background and the capsular serotype of the strain.

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Differential Role of CbpA and PspA in Modulation of In Vitro CXC Chemokine Responses of Respiratory Epithelial Cells to Infection with Streptococcus pneumoniae

Infection and Immunity ◽

10.1128/iai.00954-06 ◽

2006 ◽

Vol 74 (12) ◽

pp. 6739-6749 ◽

Cited By ~ 13

Author(s):

Rikki M. A. Graham ◽

James C. Paton

Keyword(s):

Streptococcus Pneumoniae ◽

Epithelial Cells ◽

Deletion Mutant ◽

Protein A ◽

A549 Cells ◽

Respiratory Pathogens ◽

Respiratory Epithelial Cells ◽

Cxc Chemokine ◽

Respiratory Epithelial

ABSTRACTRespiratory epithelial cells play an active part in the host response to respiratory pathogens, such asStreptococcus pneumoniae, by releasing chemokines responsible for neutrophil recruitment. In order to investigate the role of specific pneumococcal virulence factors in eliciting CXC chemokine responses, type II pneumocytes (A549) and nasopharyngeal cells (Detroit-562) were infected withS. pneumoniaeD39 or mutants lacking choline-binding protein A (CbpA), pneumococcal surface protein A (PspA), or specific domains thereof. In response to wild-type D39, both A549 and Detroit-562 cells showed a significant increase in CXC chemokine mRNA and interleukin-8 protein. This response was increased twofold when acbpAdeletion mutant (ΔCbpA) was used, suggesting that CbpA inhibits CXC chemokine induction. All three N-terminal domains of CbpA are required for this effect, as in-frame deletion of the respective region ofcbpAhad the same effect on the CXC chemokine response as deletion ofcbpAaltogether. Infection with apspAdeletion mutant (ΔPspA) led to a twofold decrease in the CXC chemokine response of A549 but not Detroit-562 cells, compared to infection with D39 at 2 h. Thus, PspA appears to have the ability to stimulate early CXC chemokine release from A549 cells. Deletion of the region ofpspAencoding the first N-terminal α-helical domain reduced the ability ofS. pneumoniaeto elicit a chemokine response to the same degree as deletion ofpspAaltogether. Thus, the N termini of CbpA and PspA exert differential effects on CXC chemokine induction in epithelial cells infected withS. pneumoniae.

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Role of the cystic fibrosis transmembrane conductance regulator in internalization of Pseudomonas aeruginosa by polarized respiratory epithelial cells

Cellular Microbiology ◽

10.1111/j.1462-5822.2004.00380.x ◽

2004 ◽

Vol 6 (6) ◽

pp. 521-533 ◽

Cited By ~ 27

Author(s):

Katharine E. A. Darling ◽

Ann Dewar ◽

Thomas J. Evans

Keyword(s):

Cystic Fibrosis ◽

Pseudomonas Aeruginosa ◽

Epithelial Cells ◽

Transmembrane Conductance Regulator ◽

Transmembrane Conductance ◽

Respiratory Epithelial Cells ◽

Respiratory Epithelial ◽

Cystic Fibrosis Transmembrane

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Role of Xanthine Oxidase Activation and Reduced Glutathione Depletion in Rhinovirus Induction of Inflammation in Respiratory Epithelial Cells

Journal of Biological Chemistry ◽

10.1074/jbc.m805766200 ◽

2008 ◽

Vol 283 (42) ◽

pp. 28595-28606 ◽

Cited By ~ 34

Author(s):

Alberto Papi ◽

Marco Contoli ◽

Pierluigi Gasparini ◽

Laura Bristot ◽

Michael R. Edwards ◽

...

Keyword(s):

Epithelial Cells ◽

Xanthine Oxidase ◽

Reduced Glutathione ◽

Glutathione Depletion ◽

Respiratory Epithelial Cells ◽

Respiratory Epithelial

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Ceramide-dependent PP2A regulation of TNFα-induced IL-8 production in respiratory epithelial cells

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.90516.2008 ◽

2009 ◽

Vol 296 (5) ◽

pp. L849-L856 ◽

Cited By ~ 34

Author(s):

Timothy T. Cornell ◽

Vania Hinkovska-Galcheva ◽

Lei Sun ◽

Qing Cai ◽

Marc B. Hershenson ◽

...

Keyword(s):

Epithelial Cells ◽

Transcriptional Activation ◽

De Novo ◽

Respiratory Epithelial Cells ◽

Subsequent Activation ◽

Or Gene ◽

Pathway Inhibition ◽

Respiratory Epithelial ◽

Ceramide Accumulation

IL-8 is a key mediator in the pathophysiology of acute lung injury. TNFα stimulates IL-8 production in respiratory epithelial cells by activating both the NF-κB and MAP kinase pathways. The precise mechanism by which these pathways are downregulated to terminate IL-8 production remains unclear. We studied the regulatory role of the serine/threonine phosphatase, PP2A, on the signaling pathways involved in IL-8 production from respiratory epithelial cells. Inhibition of PP2A using okadaic acid or gene knockdown using siRNA resulted in an augmentation of TNFα-induced IL-8 production. We also found that PP2A inhibition resulted in prolonged activation of JNK, p38, and ERK resulting in both increased transcriptional activation of the IL-8 promoter and posttranscriptional stabilization of IL-8 mRNA. Because TNFα had been shown to activate ceramide accumulation, and separate studies had linked ceramide with activation of PP2A, we hypothesized the pathway of TNFα-inducing ceramide to activate PP2A comprised an endogenous regulatory pathway. Inhibition of the immediate sphingomyelinase-dependent pathway as well as the de novo synthesis pathway of ceramide production reduced serine/threonine phosphatase activity and augmented IL-8 production. These data suggest that ceramide plays a role in activating PP2A to terminate ongoing IL-8 production. In summary, our data suggest that in respiratory epithelium, TNFα induces ceramide accumulation, resulting in subsequent activation of PP2A, which targets those kinases responsible for transcriptional activation of IL-8.

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