Respiratory Research · 2016 · 24 citations · 34 references
Life SciencesImmunologyPathobiologyInflammationInnate ImmunityMucosal ImmunologyAcid-base BalanceAcid-base RegulationMucosal InflammationRespiratory DiseaseAirway Inflammation ModulationCell Viability AssaysCytokine Expression RegulationCytokine-induced Gene ExpressionInflammatory Cytokine EffectsInflammatory Cytokine ProductionInflammatory Cytokine SecretionPro-inflammatory Cytokine Expression
BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: AEC inflammatory responses to bacterial stimuli is markedly reduced in a mildly acidic environment.
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Mutation of the mouse klotho gene leads to a syndrome resembling ageing.
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Alejandro A. Pezzulo, Xiao Xiao Tang, Mark J. Hoegger et al. · Nature · 2012 · 807 citations · Full text