In Vitro Effects of Acid and Pepsin on Mouse Middle Ear Epithelial Cell Viability and MUC5B Gene Expression

Block, Bradley B.; Kuo, E. Y.; Zalzal, Habib G.; Escobar, Hugo Murua; Rose, Mary C.; Preciado, Diego

doi:10.1001/archoto.2009.199

Cited by 12 publications

(10 citation statements)

References 32 publications

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“…16 One possible pathophysiologic mechanism of extraesophageal reflux disease (EERD)-related otitis media is eustachian tube dysfunction. This may be a result from a combination of factors, including inflammation of the mucosa from the corrosive property of gastric contents, particularly pepsin, acid, and bile acid [17][18][19][20][21] ; however, to our knowledge, the direct link between the presence of pepsin and inflammation in the middle ear has not been investigated. Our previous finding that purulent effusion and mucoid effusions were more likely to be positive for pepsin may suggest an association.…”

mentioning

confidence: 98%

The Role of Gastric Pepsin in the Inflammatory Cascade of Pediatric Otitis Media

O’Reilly

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et al. 2015

JAMA Otolaryngol Head Neck Surg

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mentioning

confidence: 98%

The Role of Gastric Pepsin in the Inflammatory Cascade of Pediatric Otitis Media

O’Reilly

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Tonb

et al. 2015

JAMA Otolaryngol Head Neck Surg

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“…For example, incubation of neurons and glial cells under pH 5.0 for 1 h decreased the number of viable cells to <50% (Nedergaard et al 1991), and mouse epithelial cells demonstrated a significantly decreased cell viability in an acidic dose-dependent manner after 1-h incubation (Block et al 2010) and also Chinese hamster ovary (CHO) cells exposed to low pH showed cytotoxicity in a time- and pH-dependent manner (Rotin et al 1986). In our study, an acidic pH of <6.5 similarly led to decreased viability in human bronchial epithelial cells (BEAS-2B) (Table 1).…”

Section: Discussionmentioning

confidence: 99%

Acidic cellular microenvironment modifies carcinogen-induced DNA damage and repair

et al. 2016

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Chronic inflammation creates an acidic microenvironment, which plays an important role in cancer development. To investigate how low pH changes the cellular response to the carcinogen benzo[a]pyrene (B[a]P), we incubated human pulmonary epithelial cells (A549 and BEAS-2B) with nontoxic doses of B[a]P using culturing media of various pH’s (extracellular pH (pHe) of 7.8, 7.0, 6.5, 6.0 and 5.5) for 6, 24 and 48 h. In most incubations (pHe 7.0–6.5), the pH in the medium returned to the physiological pH 7.8 after 48 h, but at the lowest pH (pHe < 6.0), this recovery was incomplete. Similar changes were observed for the intracellular pH (pHi). We observed that acidic conditions delayed B[a]P metabolism and at t = 48 h, and the concentration of unmetabolized extracellular B[a]P and B[a]P-7,8-diol was significantly higher in acidic samples than under normal physiological conditions (pHe 7.8) for both cell lines. Cytochrome P450 (CYP1A1/CYP1B1) expression and its activity (ethoxyresorufin-O-deethylase activity) were repressed at low pHe after 6 and 24 h, but were significantly higher at t = 48 h. In addition, a DNA repair assay showed that the incision activity was ~80% inhibited for 6 h at low pHe and concomitant exposure to B[a]P. However, at t = 48 h, the incision activity recovered to more than 100% of the initial activity observed at neutral pHe. After 48 h, higher B[a]P-DNA adduct levels and γ-H2AX foci were observed at low pH samples than at pHe 7.8. In conclusion, acidic pH delayed the metabolism of B[a]P and inhibited DNA repair, ultimately leading to increased B[a]P-induced DNA damage.Electronic supplementary materialThe online version of this article (doi:10.1007/s00204-016-1907-4) contains supplementary material, which is available to authorized users.

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“…Common to all anatomic areas where this respiratory epithelium is found is a need to act as a protective barrier to underlying tissues from damage and injury induced by bacterial and viral pathogens. In addition, other causes of middle ear epithelial injury and inflammation have been studied, including environmental agents such as tobacco smoke or internal agents such as pepsin . When confronted with potential injury from such agents, this respiratory epithelium undergoes predictable responses regardless of the potential offending agent.…”

Section: Discussionmentioning

confidence: 99%

Dexamethasone modulation ofMUC5ACandMUC2gene expression in a generalized model of middle ear inflammation

2015

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Objective To examine the effect of dexamethasone on basal and pro-inflammatory cytokines induced gel forming mucin expression in human middle ear epithelium culture (HMEEC-1). Methods HMEEC-1 was exposed to pro-inflammatory cytokines, TNF-α and IL-1β to identify optimal mucin induction. The HMEEC-1 was incubated with dexamethasone in the steady state and in the presence of pro-inflammatory cytokine stimulation. Expression of MUC2 and MUC5AC was determined by quantitative PCR. Results Pro-inflammatory cytokines, TNF-α and IL-1β, induced MUC2 and MUC5AC expression in HMEEC-1. Dexamethasone reduced steady state mRNA level of MUC5AC in a time (p<0.05) and dose dependent manner (p<0.0001). MUC2 was effectively suppressed at all time-points tested (p<0.05). Temporal difference between dexamethasone suppression of MUC2 and MUC5AC was demonstrated. Dexamethasone inhibits the pro-inflammatory cytokine induced expression of both MUC2 and MUC5AC. Conclusion This work provides a conclusive picture of the ability of using glucocorticoids to down-regulate mucin gene expression in human middle ear epithelium using a generalizable model of inflammation which is applicable to multiple potential causes of middle ear epithelium mucosal hypertrophy. This data adds to the promising potential of future interventions for patients with chronic otitis media.

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In Vitro Effects of Acid and Pepsin on Mouse Middle Ear Epithelial Cell Viability and MUC5B Gene Expression

Cited by 12 publications

References 32 publications

The Role of Gastric Pepsin in the Inflammatory Cascade of Pediatric Otitis Media

The Role of Gastric Pepsin in the Inflammatory Cascade of Pediatric Otitis Media

Acidic cellular microenvironment modifies carcinogen-induced DNA damage and repair

Dexamethasone modulation ofMUC5ACandMUC2gene expression in a generalized model of middle ear inflammation

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