Comparative metabolomics analysis of bronchial epithelium during barrier establishment after allergen exposure

Abstract

Background Several studies have shown a correlation between an altered metabolome and respiratory allergies. The epithelial barrier hypothesis proposes that an epithelial barrier dysfunction can result in allergic diseases development. Der p 1 allergen from house dust mite is a renowned epithelial barrier disruptor and allergy initiator due to its cysteine‐protease activity. Here, we compared the metabolic profile of the bronchial epithelium exposed or not to Der p 1 during barrier establishment to understand its active role in allergy development. Methods Calu‐3 cells were cultivated in air‐liquid interface cultures and exposed to either Der p 1 or Ole e 1 allergens during barrier establishment. The comparative metabolomics analysis of apical and basolateral media were performed using liquid chromatography and capillary electrophoresis both coupled to mass spectrometry. Results We showed that epithelial barrier disruption by Der p 1 was associated with a specific metabolic profile, which was highly dependent on the state of the epithelium at the time of contact. Moreover, an apical‐basolateral distribution of the metabolites was also observed, indicating a compartmentalization of the response with differential metabolic patterns. A number of metabolites were changed by Der p 1, mainly related to amino acids metabolism, such as L‐arginine, L‐kynurenine and L‐methionine. Conclusion This work is the first report on the metabolic response in human bronchial epithelial cells associated with cysteine‐protease Der p 1 activity, which could contribute to allergy development. Moreover, it supports a reformulated epithelial barrier hypothesis that might help to explain allergies and their increasing prevalence.

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“…The complex of different chemical and biological agents, which humans are daily exposed to, is known as the "exposome" [187] and includes microorganisms, pollution, hygiene-derived products, HDM, natural toxins, and food additives. The exposure to these factors alters the cell functions and favors the allergic response activation [188,189].…”

The New Paradigm: The Role of Proteins and Triggers in the Evolution of Allergic Asthma

“…The complex of different chemical and biological agents that humans are exposed to daily is known as the “exposome” [ 187 ] and includes microorganisms, pollution, hygiene-derived products, HDM, natural toxins, and food additives. The exposure to these factors alters cell function and favors the allergic response activation [ 188 , 189 ].…”

Interleukin-13 Treatment of Living Lung Tissue Model Alters the Metabolome and Proteome—A Nano-DESI MS Metabolomics and Shotgun Proteomics Study

“…Metabolomics is a powerful tool that can reveal altered metabolic pathways due to stress conditions such as pathogenesis or drug treatment [22][23][24]. Previous studies have investigated metabolome alterations in ALI cells [25][26][27]. In such studies, the tissue model is exposed to drugs or smoke for one or several time periods.…”