Abstract
Objective This study is aimed at investigating the role of substance P (SP) in the development of asthma. Methods The Gene Expression Omnibus (GEO) database was used to characterize SP expression in allergic rhinitis (AR) and asthma. Peripheral blood was collected from patients with asthma or AR. The expression of relevant cytokines and neuropeptides was measured. Enzyme-linked immunosorbent assay (ELISA) was also performed. The mast cell line LAD2 and the lung bronchial epithelial cell line BEAS-2B were treated with different concentrations of SP concentration. Then, the qRT-PCR method was used to determine the mRNA expression. Furthermore, p38 and p65 and their associated phosphorylated proteins (p-p38 and p-p65) were further validated by western blotting. Result Clinical and GSE75011 data analysis suggested that MyD88 expression was upregulated in AR and asthma. Through the gene set variation analysis (GSVA), MyD88-related pathways were noticed and further investigated. ELISA results suggested that the SP expression was significantly increased in AR and asthma and IL-10 expression was decreased, whereas the expression of IL-6, IL-17A, IL-23, and TGF-β expressions increased. The mast cell line LAD2 was treated with different SP concentrations, and ELISA results showed that the expression of IL-6, IL-17A, IL-23, and TGF-β in the cell supernatant gradually increased with increasing SP concentrations, whereas that of IL-10 decreased. The lung bronchial epithelial cell line BEAS-2B was treated with different SP concentrations, and the expression of myeloid differentiation factor 88 (MyD88) and its related proteins was elevated. The expression of p38 and p-p38 proteins was elevated after SP treatment, and their expression levels elevated as SP concentrations increased. Finally, MyD88 expression at the single-cell level was also demonstrated. Conclusion SP may affect the cytokine expression through the MyD88 pathway, thereby influencing Th17/Treg differentiation and eventually participating in the pathological process of asthma and AR. There are many pathological similarities between allergic rhinitis (AR) and bronchial asthma. In the present study, SP was found to possibly activate downstream inflammatory signaling pathways via MyD88, thereby affecting Th17/Treg differentiation and ultimately participating in the pathological process of asthma and AR.
Highlights
There are many pathological similarities between allergic rhinitis (AR) and bronchial asthma [1]
The GSE75011 dataset from the Gene Expression Omnibus (GEO) database was used for this study, which included 40 asthma patients, 25 AR patients, and 15 normal individuals [21]
substance P (SP) in the serum was measured via Enzyme-linked immunosorbent assay (ELISA), and a significant increase in SP expression was found in patients with AR (Figure 1(b))
Summary
There are many pathological similarities between allergic rhinitis (AR) and bronchial asthma [1]. AR is an allergic reaction of the nasal mucosa triggered by an allergen, whose treatment is multimodal. It has been found to be associated with poor treatment outcome of deviated septum [1, 2]. Bronchial asthma (hereinafter referred to as asthma) is a chronic airway inflammatory disease [3]. Both diseases occur in allergic and pediatric populations, and AR is generally mild, some studies suggest that AR has a high potential to trigger bronchial asthma [4].
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