Weakly acidic pH reduces inflammatory cytokine expression in airway epithelial cells

Abstract

BackgroundAspiration 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.MethodsUsing 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.ResultsIL-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.ConclusionAEC inflammatory responses to bacterial stimuli is markedly reduced in a mildly acidic environment.

Distinct Immune Responses Elicited From Cervicovaginal Epithelial Cells by Lactic Acid and Short Chain Fatty Acids Associated With Optimal and Non-optimal Vaginal Microbiota

“…Furthermore, we assessed concentrations of vaginal microbiota metabolites reflective of those found in the vaginal lumen; cells present deeper within the vaginal epithelium may be exposed to different, and likely lower, concentrations of metabolites than those analyzed here. The effects of eubiotic metabolite mixtures were assessed here at pH 3.9, and although we did not find a significant immunomodulatory effect of pH 3.9 media alone on cervicovaginal cells in a previous study (Hearps et al, 2017), acidity has been shown to dampen inflammatory responses of other types of epithelial cells (Hackett et al, 2016). It therefore remains possible that low pH may be contributing to the antiinflammatory properties of the eubiotic metabolites shown here.…”

Suppression of Intestinal Epithelial Cell Chemokine Production by Lactobacillus rhamnosus R0011 and Lactobacillus helveticus R0389 Is Mediated by Secreted Bioactive Molecules

“…Acidification of culture medium has been associated with diminished monocyte activity and TNFα secretion as a result of a decrease in the glycolytic flux in macrophages ( 51 ). Moreover, culture medium acidification results in reduction of IL-6 and IL-8 production from airway epithelial cells challenged with or without LPS ( 52 ). Overall this suggests a stimulus-dependent impact of acidification, which may contribute to the bioactivity of the Lr-CFS in HT-29 IECs challenged with IL-1β.…”

VISTA: A novel immunotherapy target for normalizing innate and adaptive immunity

“…From a disease perspective, the microenvironment of some tumor types have been reported to be as low as pH 6.44 [58,59], and the ionic environment in the TME can dictate the fate of anti-tumor T cell immunity [60]. The impact of low pH on driving pathologic inflammation has been also been long appreciated [61][62][63]. The concept of immunoregulatory protein interactions being governed by the pH of the host tissue is a valuable one.…”