Pro-inflammatory mediator responses from neonatal airway epithelial cells and early childhood wheeze

Steve Turner, David Miller, Garry M Walsh, Alison Scaife, Ultan F. Power, Michael D. Shields, Graham Devereux

Research output: Contribution to journalArticle

2 Citations (Scopus)
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Abstract

Background: Airway epithelial cell (AEC) function differs between children with and without asthma. Here, we associated neonatal AEC function with asthma symptoms at 4 years of age. Methods: Nasal AEC were collected from neonates within 48 h of birth. Cells were cultured and stimulated with tumor necrosis factor alpha/interleukin-1 beta (TNFα/IL-1β), lipopolysaccharide (LPS), or house dust mite (HDM). Absolute concentrations of pro-inflammatory mediators in the culture supernatant were quantified and expressed as median [interquartile range] in pg/mg protein. A parent-completed respiratory questionnaire was returned when the child was 4 years old. Results: AEC were successfully cultured in 139 neonates, of whom 120 were contacted at 4 years and 91 (76%) questionnaires were returned. Sixteen children had wheezed ever and 11 had recent wheeze. At birth, when compared to those with no recent wheeze, supernatants from cultured neonatal AEC from the children with recent wheeze had reduced median IL-8 (CXCL8) release after treatment with culture medium alone (P = 0.049), with TNFα/IL-1β (P < 0.001) and LPS (P = 0.004). Additionally, and when compared to those with no recent wheeze, 4 year olds with recent wheeze had reduced neonatal AEC release of IL-6 (P = 0.013), GMCSF (P = 0.012), and ICAM-1 (P = 0.017) after treatment with TNFα/IL-1β and reduced release of ICAM-1 (P = 0.038) and RANTES (P = 0.042) after treatment with HDM. Conclusions: Abnormalities in AEC function are present at birth before the onset of childhood wheeze. The relationship between reduced AEC function at birth and wheeze at 4 years was not exclusive, suggesting that post-natal factors are required for the AEC abnormality to translate into symptoms.
Original languageEnglish
Pages (from-to)10-16
Number of pages16
JournalPediatric Pulmonology
Volume53
Issue number1
Early online date14 Nov 2017
DOIs
Publication statusPublished - Jan 2018

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Epithelial Cells
Interleukin-1beta
Parturition
Pyroglyphidae
Tumor Necrosis Factor-alpha
Intercellular Adhesion Molecule-1
Lipopolysaccharides
Asthma
Newborn Infant
Chemokine CCL5
Interleukin-8
Nose
Culture Media
Cultured Cells
Interleukin-6
Therapeutics
Proteins

Keywords

  • Asthma
  • Epithelial cell
  • Longitudinal study
  • Neonate

Cite this

Pro-inflammatory mediator responses from neonatal airway epithelial cells and early childhood wheeze. / Turner, Steve; Miller, David; Walsh, Garry M; Scaife, Alison; Power, Ultan F.; Shields, Michael D.; Devereux, Graham.

In: Pediatric Pulmonology, Vol. 53, No. 1, 01.2018, p. 10-16.

Research output: Contribution to journalArticle

Turner, Steve ; Miller, David ; Walsh, Garry M ; Scaife, Alison ; Power, Ultan F. ; Shields, Michael D. ; Devereux, Graham. / Pro-inflammatory mediator responses from neonatal airway epithelial cells and early childhood wheeze. In: Pediatric Pulmonology. 2018 ; Vol. 53, No. 1. pp. 10-16.
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abstract = "Background: Airway epithelial cell (AEC) function differs between children with and without asthma. Here, we associated neonatal AEC function with asthma symptoms at 4 years of age. Methods: Nasal AEC were collected from neonates within 48 h of birth. Cells were cultured and stimulated with tumor necrosis factor alpha/interleukin-1 beta (TNFα/IL-1β), lipopolysaccharide (LPS), or house dust mite (HDM). Absolute concentrations of pro-inflammatory mediators in the culture supernatant were quantified and expressed as median [interquartile range] in pg/mg protein. A parent-completed respiratory questionnaire was returned when the child was 4 years old. Results: AEC were successfully cultured in 139 neonates, of whom 120 were contacted at 4 years and 91 (76{\%}) questionnaires were returned. Sixteen children had wheezed ever and 11 had recent wheeze. At birth, when compared to those with no recent wheeze, supernatants from cultured neonatal AEC from the children with recent wheeze had reduced median IL-8 (CXCL8) release after treatment with culture medium alone (P = 0.049), with TNFα/IL-1β (P < 0.001) and LPS (P = 0.004). Additionally, and when compared to those with no recent wheeze, 4 year olds with recent wheeze had reduced neonatal AEC release of IL-6 (P = 0.013), GMCSF (P = 0.012), and ICAM-1 (P = 0.017) after treatment with TNFα/IL-1β and reduced release of ICAM-1 (P = 0.038) and RANTES (P = 0.042) after treatment with HDM. Conclusions: Abnormalities in AEC function are present at birth before the onset of childhood wheeze. The relationship between reduced AEC function at birth and wheeze at 4 years was not exclusive, suggesting that post-natal factors are required for the AEC abnormality to translate into symptoms.",
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note = "The authors would like to thank the study participants and their parents. The recruitment and sampling of this cohort was funded by the Chief Scientist Office, Edinburgh, UK (CAF/10/06). The follow up received no funding.",
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AU - Turner, Steve

AU - Miller, David

AU - Walsh, Garry M

AU - Scaife, Alison

AU - Power, Ultan F.

AU - Shields, Michael D.

AU - Devereux, Graham

N1 - The authors would like to thank the study participants and their parents. The recruitment and sampling of this cohort was funded by the Chief Scientist Office, Edinburgh, UK (CAF/10/06). The follow up received no funding.

PY - 2018/1

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N2 - Background: Airway epithelial cell (AEC) function differs between children with and without asthma. Here, we associated neonatal AEC function with asthma symptoms at 4 years of age. Methods: Nasal AEC were collected from neonates within 48 h of birth. Cells were cultured and stimulated with tumor necrosis factor alpha/interleukin-1 beta (TNFα/IL-1β), lipopolysaccharide (LPS), or house dust mite (HDM). Absolute concentrations of pro-inflammatory mediators in the culture supernatant were quantified and expressed as median [interquartile range] in pg/mg protein. A parent-completed respiratory questionnaire was returned when the child was 4 years old. Results: AEC were successfully cultured in 139 neonates, of whom 120 were contacted at 4 years and 91 (76%) questionnaires were returned. Sixteen children had wheezed ever and 11 had recent wheeze. At birth, when compared to those with no recent wheeze, supernatants from cultured neonatal AEC from the children with recent wheeze had reduced median IL-8 (CXCL8) release after treatment with culture medium alone (P = 0.049), with TNFα/IL-1β (P < 0.001) and LPS (P = 0.004). Additionally, and when compared to those with no recent wheeze, 4 year olds with recent wheeze had reduced neonatal AEC release of IL-6 (P = 0.013), GMCSF (P = 0.012), and ICAM-1 (P = 0.017) after treatment with TNFα/IL-1β and reduced release of ICAM-1 (P = 0.038) and RANTES (P = 0.042) after treatment with HDM. Conclusions: Abnormalities in AEC function are present at birth before the onset of childhood wheeze. The relationship between reduced AEC function at birth and wheeze at 4 years was not exclusive, suggesting that post-natal factors are required for the AEC abnormality to translate into symptoms.

AB - Background: Airway epithelial cell (AEC) function differs between children with and without asthma. Here, we associated neonatal AEC function with asthma symptoms at 4 years of age. Methods: Nasal AEC were collected from neonates within 48 h of birth. Cells were cultured and stimulated with tumor necrosis factor alpha/interleukin-1 beta (TNFα/IL-1β), lipopolysaccharide (LPS), or house dust mite (HDM). Absolute concentrations of pro-inflammatory mediators in the culture supernatant were quantified and expressed as median [interquartile range] in pg/mg protein. A parent-completed respiratory questionnaire was returned when the child was 4 years old. Results: AEC were successfully cultured in 139 neonates, of whom 120 were contacted at 4 years and 91 (76%) questionnaires were returned. Sixteen children had wheezed ever and 11 had recent wheeze. At birth, when compared to those with no recent wheeze, supernatants from cultured neonatal AEC from the children with recent wheeze had reduced median IL-8 (CXCL8) release after treatment with culture medium alone (P = 0.049), with TNFα/IL-1β (P < 0.001) and LPS (P = 0.004). Additionally, and when compared to those with no recent wheeze, 4 year olds with recent wheeze had reduced neonatal AEC release of IL-6 (P = 0.013), GMCSF (P = 0.012), and ICAM-1 (P = 0.017) after treatment with TNFα/IL-1β and reduced release of ICAM-1 (P = 0.038) and RANTES (P = 0.042) after treatment with HDM. Conclusions: Abnormalities in AEC function are present at birth before the onset of childhood wheeze. The relationship between reduced AEC function at birth and wheeze at 4 years was not exclusive, suggesting that post-natal factors are required for the AEC abnormality to translate into symptoms.

KW - Asthma

KW - Epithelial cell

KW - Longitudinal study

KW - Neonate

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DO - 10.1002/ppul.23915

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