title: Weakly acidic pH reduces inflammatory cytokine expression in airway epithelial cells.
abstract: Aspiration lung disease (ALD) is a common cause of respiratory morbidity in children and adults with severe neurodisability (sND). Recent studies suggest that chronic microaspiration of gastric contents is associated with mild rather than low, airway acidification. We investigated inflammatory responses to infection by airway epithelial cells (AECs) exposed to weakly acidic media.
  
  
  
  Using pH measurements from children with sND at high risk of ALD as a guide, we incubated AECs in weakly acidic (pH5.5-7.4) media alone; in combination with lipopolysaccharide (LPS); or prior to LPS stimulation at normal pH. Interleukin (IL) -6 and IL-8 expression were measured.
  
  
  
  IL-6/8 expression in AECs simultaneously exposed to weakly acidic media and LPS for 4 h was reduced with no effect on cell viability. Pre-incubation of AECs at weakly acidic pH also reduced subsequent LPS-induced cytokine expression. Suppression of inflammation was greatest at lower pHs (pH 5.5-6.0) for prolonged periods (16/24 h), but this also adversely affected cell viability.
  
  
  
  AEC inflammatory responses to bacterial stimuli is markedly reduced in a mildly acidic environment.
authors.affiliation: Department of Women's and Children's Health, Institute of Translational Medicine, University of Liverpool, Liverpool, UK.
authors.forename: A P
authors.initials: AP
authors.lastname: Hackett
authors.affiliation: Alder Hey Children's Hospital NHS Foundation Trust, Eaton Rd, Liverpool, UK.
authors.forename: R E
authors.initials: RE
authors.lastname: Trinick
authors.affiliation: Department of Women's and Children's Health, Institute of Translational Medicine, University of Liverpool, Liverpool, UK.
authors.forename: K
authors.initials: K
authors.lastname: Rose
authors.affiliation: Department of Women's and Children's Health, Institute of Translational Medicine, University of Liverpool, Liverpool, UK.
authors.forename: B F
authors.initials: BF
authors.lastname: Flanagan
authors.affiliation: Department of Women's and Children's Health, Institute of Translational Medicine, University of Liverpool, Liverpool, UK. mcnamp@liverpool.ac.uk.|Alder Hey Children's Hospital NHS Foundation Trust, Eaton Rd, Liverpool, UK. mcnamp@liverpool.ac.uk.
authors.forename: P S
authors.initials: PS
authors.lastname: McNamara
mesh_terms: D002460:Cell Line; D002470:Cell Survival; D002493:Central Nervous System Diseases / Q000150:complications* / Q000276:immunology / Q000378:metabolism; D015536:Down-Regulation; D004847:Epithelial Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D018836:Inflammation Mediators / Q000276:immunology / Q000378:metabolism*; D015850:Interleukin-6 / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D016209:Interleukin-8 / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008168:Lung / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D063466:Respiratory Aspiration of Gastric Contents / Q000209:etiology* / Q000276:immunology / Q000503:physiopathology; D013997:Time Factors
chemical_list: C508606:CXCL8 protein, human; C508600:IL6 protein, human; D018836:Inflammation Mediators; D015850:Interleukin-6; D016209:Interleukin-8; D008070:Lipopolysaccharides
keywords: Airway epithelial cells; BAL; Inflammation; Interleukin-6; Interleukin-8; Lipopolysaccharide; Neurodisability; Reflux-aspiration