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Inhibition of asthma-related immunological responses in mast cells and Th2 cell lines by cultured epithelial cell lines

Timothy Powell, Will Sargent, Rahul Shrimanker, Linda Stoeger, Ian Pavord
European Respiratory Journal 2016 48: PA4663; DOI: 10.1183/13993003.congress-2016.PA4663
Timothy Powell
1Respiratory Medicine Unit, University of Oxford, Oxford, United Kingdom
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Will Sargent
1Respiratory Medicine Unit, University of Oxford, Oxford, United Kingdom
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Rahul Shrimanker
1Respiratory Medicine Unit, University of Oxford, Oxford, United Kingdom
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Linda Stoeger
1Respiratory Medicine Unit, University of Oxford, Oxford, United Kingdom
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Ian Pavord
1Respiratory Medicine Unit, University of Oxford, Oxford, United Kingdom
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Abstract

Previous studies have shown that constitutive and IgE-mediated histamine production by human lung mast cells is inhibited by a transferable factor produced by the airway epithelium. We investigated the effect of co-culture of epithelial cells with mast cell lines. We also measured the effect of co-culture of epithelial cell lines and TH2 cells on interleukin (IL)-13 production. A549 or BEAS-2B cells were grown to confluence overnight and LAD2, HMC1.2 or human ex-vivo T-cells added. For transwell experiments epithelial cells were added to a 24w plate for 16h and mast cells added to the insert. Wells and transwell insert supernatants were harvested and mediator release quantified by histamine or IL-13 ELISA. Mast cell surface expression of ckit was measured by flow cytometry. Constitutive histamine production by HMC1.2 was reduced from 191 ± 13 ng/106 cells by 60.9% (95% CI 54.1, 67.8; p<0.0001) when co-cultured with A549 and 21% (95% CI 14.2, 28.1; p<0.0001) with BEAS-2B cells. Similar findings were seen with the LAD2 mast cell line. Constitutive IL-13 production by TH2 cells was reduced from 18000 ± 1800 pg/106 cells by 68.6% (95% CI 62.0, 75.1; P<0.0001) by A549 and 59.9% (95% CI 53.3, 66.5; p<0.0001) by BEAS-2B. Epithelial inhibition was similar when cells were separated by a transwell suggesting involvement of a soluble factor. Surface expression of ckit measured by flow cytometry was also reduced in the presence of epithelial cells. Epithelial cell lines inhibit a range of asthma-related mediators and reduce the cell surface expression of ckit. Deficiency in this process may be important in the pathogenesis of the abnormal airway responses seen in asthma.

  • Asthma - mechanism
  • Immunology
  • Epithelial cell
  • Copyright ©the authors 2016
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Inhibition of asthma-related immunological responses in mast cells and Th2 cell lines by cultured epithelial cell lines
Timothy Powell, Will Sargent, Rahul Shrimanker, Linda Stoeger, Ian Pavord
European Respiratory Journal Sep 2016, 48 (suppl 60) PA4663; DOI: 10.1183/13993003.congress-2016.PA4663

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Inhibition of asthma-related immunological responses in mast cells and Th2 cell lines by cultured epithelial cell lines
Timothy Powell, Will Sargent, Rahul Shrimanker, Linda Stoeger, Ian Pavord
European Respiratory Journal Sep 2016, 48 (suppl 60) PA4663; DOI: 10.1183/13993003.congress-2016.PA4663
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