Environmental pollutant 3-methyl-4-nitrophenol promotes the expression of oncostatin M to exacerbate airway allergic inflammation.

Abstract

Asthma exacerbation is a common clinical occurrence. The causal factors are not fully understood yet. Environmental pollution is linked to asthma exacerbation. The objective of this study is to elucidate the role of 3-methyl-4-nitrophenol (MNP), an environmental pollutant, in asthma exacerbation. In this study, an airway allergy mouse model was established with ovalbumin as a specific antigen with or without the presence of MNP. The results showed that, in a mouse model, the intensity of airway allergy was significantly increased by exposure to MNP. RNAseq results showed an increase in ER stress-associated molecules and the Osm expression in airway epithelial cells of mice with airway allergy. Exposure of epithelial cells to MNP in culture induced the expression of OSM and ER stress associated molecules. The OSM receptor was expressed by macrophages. OSM could drive macrophages to produce TNF-α. Inhibition of PERK, one of the key molecules of ER stress, or depletion of OSM receptor in macrophages, could effectively attenuate the MNP/OVA protocol induced airway allergy. To sum up, by promoting ER stress, environmental pollutant MNP can cause airway epithelial cells to produce OSM. The latter induces macrophages to produce TNF-α, which can exacerbate airway allergy.