The impact of early life stress on airway remodeling and severe asthma related gene profile in mice

Aim and objective: Neonatal and infants may suffer from stress due to many reasons. Stress may be unavoidable nowadays and has a negative impact which may be the initiator of different diseases. Early life stress influences the airway, which may result in asthma at any stage of life; it also impacts the severity of asthma and the airway structure. Chronic stress increases cortisol levels via Hypothalamic-pituitary-adrenal (HPA) axis activation. Imbalanced cortisol increases the pro-inflammatory cytokines in the blood, which induce inflammation. In this study, mRNA expression of the airway remodeling and severe asthma-related genes were investigated in the early-life stressed mice and in vitro chronic low and high-stress mimic conditions by administrating dexamethasone. Methods: In this study, mRNA expression of the airway remodeling and severe asthma-related genes were investigated in the early-life stressed mice and in vitro chronic low and high-stress mimic conditions. The mice were separated the mother 3 hours daily from postnatal days 1-14 (PND1-PND14), and blood was collected on PND35. The administration of chronic low (10nM) and chronic high (100nM) of dexamethasone for a duration of five days in vitro Beas 2B cell to produce chronic low and chronic high stress mimic condition. . RNA was extracted from the blood of mice and human bronchial epithelial cell Beas 2B followed by the synthesis of complementary DNA (cDNA). RT-PCR was performed to evaluate the mRNA expression level. Graphical presentation was performed in Graph pad prism 8.4.3. Results: In vivo results shows that early life stress has an elevation of the Postn, Chi3l1 & Ccl11 genes, which are related to asthma severity and airway remodeling. In vitro, chronic low and high stress has been found to have an impact on the expression of IL-33 levels by increasing significantly (fold change 4.9 and 3.28 respectively). Conclusion: Exposure to stress during early life has been found to have a significant impact on the development of asthma and the remodeling of airways. Keywords: Early life stress, Chronic Stress, Airway remodeling, Severe asthma, dexamethasone.