Abstract
Both epidemiological and laboratory evidence indicate a significant relationship between formaldehyde (FA) exposure and allergic asthma. However, the mechanisms underlying the relationship remain unclear. Research has demonstrated that endoplasmic reticulum (ER) stress is closely associated with the onset of allergic asthma. Nonetheless, it has yet to be established whether FA exposure exacerbates allergic asthma by activating ER stress. To systematically investigate the exacerbation of allergic asthma-like symptoms due to FA exposure (0.5 mg/m3) in Balb/c mice, we assessed lung function and histopathology, serum immunoglobulin levels, neuropeptide substance P (SP) and calcitonin gene-related peptide (CGRP) levels, Th2 (IL-4, IL-5, IL-13) and Th17 (IL-22, IL-17A) cytokine levels and biomarkers of the ER stress pathway (IRE1α, PERK, and ATF-6). Additionally, we employed the ER stress antagonist phenylbutyric acid (4-PBA) to confirm the mediating role of ER stress in FA-aggravated allergic asthma. Our findings suggest that prolonged exposure to FA increases levels of ER stress markers, SP, CGRP, Th2 and Th17 cytokines, and immunoglobulin, leading to increased airway mucus hyperplasia and airway remodeling. Furthermore, we demonstrated that blocking ER stress with 4-PBA effectively alleviated associated allergic asthma-like symptoms. In conclusion, we provide evidence that the ER stress signaling pathway plays a significant role in the exacerbation of allergic asthma due to FA exposure.
