Airway epithelial cytokine responses in childhood wheeze are independent of atopic status

Catherine M McDougall, Peter J Helms, Garry M Walsh (Corresponding Author)

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Background Airway epithelial cells (AEC) are key contributors to immune function in the lungs but little is known about their role and function in children. Objectives Having previously established that nasal AEC mediator release correlates with that of bronchial AEC, we assessed AEC responses in children with and without a history of wheeze. Methods Nasal AEC cultures were established from children (0.6–14.9 years) undergoing elective surgical procedures under general anaesthetic categorised as atopic asthmatic (n=12), virus-induced wheeze (n=8) or children without wheeze (n=32). Mediator release by AEC monolayers at passage 2 was determined by cytometric bead array assay or ELISA. Results Unstimulated AEC from children with a history of wheeze produced significantly less IL-8, IL-6, MCP-1 and G-CSF than AEC from healthy controls. There were no group differences in AEC release of VEGF, RANTES, MMP-9 or TIMP-1. After stimulation with the pro-inflammatory cytokines IL-1β and TNFα, AEC from children with current wheeze produced significantly less IL-8, IL-6 and MCP-1 than children without wheeze. Release of G-CSF, VEGF, MMP-9 and TIMP-1 did not differ between the wheeze and control group. There were no differences in mediator release between subjects with atopic asthma and those with virus-induced wheeze or between atopic and non-atopic controls. On multivariate analysis, wheeze was the only significant predictor of AEC mediator release. Conclusion & Clinical Relevance Intrinsic differences in AEC from children with a history of wheeze may reflect a defect in cytokine production in vivo or an altered state of differentiation in vitro, independent of atopic status.
Original languageEnglish
Pages (from-to)689-700
Number of pages12
JournalRespiratory Medicine
Volume109
Issue number6
Early online date14 Apr 2015
DOIs
Publication statusPublished - Jun 2015

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Cytokines
Tissue Inhibitor of Metalloproteinase-1
Granulocyte Colony-Stimulating Factor
Matrix Metalloproteinases
Interleukin-8
Vascular Endothelial Growth Factor A
Interleukin-6
Elective Surgical Procedures
Viruses
Chemokine CCL5
General Anesthetics
Interleukin-1
Nose
Multivariate Analysis
Asthma
Epithelial Cells
Enzyme-Linked Immunosorbent Assay
Lung
Control Groups

Keywords

  • airway epithelium
  • wheeze
  • children
  • mediator release

Cite this

Airway epithelial cytokine responses in childhood wheeze are independent of atopic status. / McDougall, Catherine M; Helms, Peter J; Walsh, Garry M (Corresponding Author).

In: Respiratory Medicine, Vol. 109, No. 6, 06.2015, p. 689-700.

Research output: Contribution to journalArticle

McDougall, Catherine M ; Helms, Peter J ; Walsh, Garry M. / Airway epithelial cytokine responses in childhood wheeze are independent of atopic status. In: Respiratory Medicine. 2015 ; Vol. 109, No. 6. pp. 689-700.
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abstract = "Background Airway epithelial cells (AEC) are key contributors to immune function in the lungs but little is known about their role and function in children. Objectives Having previously established that nasal AEC mediator release correlates with that of bronchial AEC, we assessed AEC responses in children with and without a history of wheeze. Methods Nasal AEC cultures were established from children (0.6–14.9 years) undergoing elective surgical procedures under general anaesthetic categorised as atopic asthmatic (n=12), virus-induced wheeze (n=8) or children without wheeze (n=32). Mediator release by AEC monolayers at passage 2 was determined by cytometric bead array assay or ELISA. Results Unstimulated AEC from children with a history of wheeze produced significantly less IL-8, IL-6, MCP-1 and G-CSF than AEC from healthy controls. There were no group differences in AEC release of VEGF, RANTES, MMP-9 or TIMP-1. After stimulation with the pro-inflammatory cytokines IL-1β and TNFα, AEC from children with current wheeze produced significantly less IL-8, IL-6 and MCP-1 than children without wheeze. Release of G-CSF, VEGF, MMP-9 and TIMP-1 did not differ between the wheeze and control group. There were no differences in mediator release between subjects with atopic asthma and those with virus-induced wheeze or between atopic and non-atopic controls. On multivariate analysis, wheeze was the only significant predictor of AEC mediator release. Conclusion & Clinical Relevance Intrinsic differences in AEC from children with a history of wheeze may reflect a defect in cytokine production in vivo or an altered state of differentiation in vitro, independent of atopic status.",
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note = "Funding This study was supported by a Medical Research Council (UK) G84/6558 Clinical Research Training Fellowship and grants from NHS Grampian and Tenovus Scotland (CMcD and GMW) NHS Grampian is 05/17; Tenovus is G05/10. Acknowledgements The authors thank Norma Cruickshank and Alison Charles, Department of Immunology, Aberdeen Royal Infirmary, for performing the IgE measurements, all the study participants and the surgical secretaries, surgeons and anaesthetists who facilitated subject recruitment and sample collection.",
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AU - Helms, Peter J

AU - Walsh, Garry M

N1 - Funding This study was supported by a Medical Research Council (UK) G84/6558 Clinical Research Training Fellowship and grants from NHS Grampian and Tenovus Scotland (CMcD and GMW) NHS Grampian is 05/17; Tenovus is G05/10. Acknowledgements The authors thank Norma Cruickshank and Alison Charles, Department of Immunology, Aberdeen Royal Infirmary, for performing the IgE measurements, all the study participants and the surgical secretaries, surgeons and anaesthetists who facilitated subject recruitment and sample collection.

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N2 - Background Airway epithelial cells (AEC) are key contributors to immune function in the lungs but little is known about their role and function in children. Objectives Having previously established that nasal AEC mediator release correlates with that of bronchial AEC, we assessed AEC responses in children with and without a history of wheeze. Methods Nasal AEC cultures were established from children (0.6–14.9 years) undergoing elective surgical procedures under general anaesthetic categorised as atopic asthmatic (n=12), virus-induced wheeze (n=8) or children without wheeze (n=32). Mediator release by AEC monolayers at passage 2 was determined by cytometric bead array assay or ELISA. Results Unstimulated AEC from children with a history of wheeze produced significantly less IL-8, IL-6, MCP-1 and G-CSF than AEC from healthy controls. There were no group differences in AEC release of VEGF, RANTES, MMP-9 or TIMP-1. After stimulation with the pro-inflammatory cytokines IL-1β and TNFα, AEC from children with current wheeze produced significantly less IL-8, IL-6 and MCP-1 than children without wheeze. Release of G-CSF, VEGF, MMP-9 and TIMP-1 did not differ between the wheeze and control group. There were no differences in mediator release between subjects with atopic asthma and those with virus-induced wheeze or between atopic and non-atopic controls. On multivariate analysis, wheeze was the only significant predictor of AEC mediator release. Conclusion & Clinical Relevance Intrinsic differences in AEC from children with a history of wheeze may reflect a defect in cytokine production in vivo or an altered state of differentiation in vitro, independent of atopic status.

AB - Background Airway epithelial cells (AEC) are key contributors to immune function in the lungs but little is known about their role and function in children. Objectives Having previously established that nasal AEC mediator release correlates with that of bronchial AEC, we assessed AEC responses in children with and without a history of wheeze. Methods Nasal AEC cultures were established from children (0.6–14.9 years) undergoing elective surgical procedures under general anaesthetic categorised as atopic asthmatic (n=12), virus-induced wheeze (n=8) or children without wheeze (n=32). Mediator release by AEC monolayers at passage 2 was determined by cytometric bead array assay or ELISA. Results Unstimulated AEC from children with a history of wheeze produced significantly less IL-8, IL-6, MCP-1 and G-CSF than AEC from healthy controls. There were no group differences in AEC release of VEGF, RANTES, MMP-9 or TIMP-1. After stimulation with the pro-inflammatory cytokines IL-1β and TNFα, AEC from children with current wheeze produced significantly less IL-8, IL-6 and MCP-1 than children without wheeze. Release of G-CSF, VEGF, MMP-9 and TIMP-1 did not differ between the wheeze and control group. There were no differences in mediator release between subjects with atopic asthma and those with virus-induced wheeze or between atopic and non-atopic controls. On multivariate analysis, wheeze was the only significant predictor of AEC mediator release. Conclusion & Clinical Relevance Intrinsic differences in AEC from children with a history of wheeze may reflect a defect in cytokine production in vivo or an altered state of differentiation in vitro, independent of atopic status.

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JO - Respiratory Medicine

JF - Respiratory Medicine

SN - 0954-6111

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