Effects of Repetitive Allergen Challenge on Expression of TGF-β, Activin -A and Its Receptor ALK4 in Nasal Mucosa of Allergic Rhinitis

Abstract

RationaleTransforming growth factor (TGF)-β and activin-A are implicated in the airway remodelling in asthma, but the role in allergic rhinitis (AR) has not been elucidated. We aimed to determine the expression of TGF-β, activin-A and its receptor activin-like kinase 4 (ALK-4) in nasal mucosa of allergic rhinitis after repetitive allergen challenge.Methods12 subjects with grass pollen-associated seasonal AR and 16 normal health controls have been studied, repetitive allergen challenge(RAC) and diluents were given the allergic patients and health groups for the total 5 doses, two biopsies were taken after 24 hours at the first (Day1) and last challenge (Day11). Immunoreactivity of Activin-A, ALK-4 and TGF-β in the biopsies was assessed by immunohistochemistry and image analysis.ResultsThere were significant higher in the numbers of Activin-A and TGF- β immunoreactive cells at day 11 after repetitive allergen challenge compared to diluents (Median [IQ range]: 43.4 (18.2-69.3) vs. 11.2 (2.9-37.5); p=0.01 for Activin-A, 29.7 (6.6-40.3) vs. 6.6 (1.2-12.3); p=0.04 for TGF-β respectively), the numbers of ALK-4 immunoreactive cells at day 11 were trend to increase compared to diluents (Median [IQ range]: 5.9 (1.3-16.4) vs. 1.4 (0.8-2.9); p=0.06). However, no significant differences in immunoreactivity of these molecules in nasal biopsies were found either between diluents and allergen challenge at day1, or compared with that of the healthy controls.ConclusionsOur data suggest that repetitive allergen challenge enhances the expression of activin-A and TGF-β in nasal mucosa of allergic rhinitis. These molecules may contribute to upper airway inflammation and remodelling in allergic rhinitis. RationaleTransforming growth factor (TGF)-β and activin-A are implicated in the airway remodelling in asthma, but the role in allergic rhinitis (AR) has not been elucidated. We aimed to determine the expression of TGF-β, activin-A and its receptor activin-like kinase 4 (ALK-4) in nasal mucosa of allergic rhinitis after repetitive allergen challenge. Transforming growth factor (TGF)-β and activin-A are implicated in the airway remodelling in asthma, but the role in allergic rhinitis (AR) has not been elucidated. We aimed to determine the expression of TGF-β, activin-A and its receptor activin-like kinase 4 (ALK-4) in nasal mucosa of allergic rhinitis after repetitive allergen challenge. Methods12 subjects with grass pollen-associated seasonal AR and 16 normal health controls have been studied, repetitive allergen challenge(RAC) and diluents were given the allergic patients and health groups for the total 5 doses, two biopsies were taken after 24 hours at the first (Day1) and last challenge (Day11). Immunoreactivity of Activin-A, ALK-4 and TGF-β in the biopsies was assessed by immunohistochemistry and image analysis. 12 subjects with grass pollen-associated seasonal AR and 16 normal health controls have been studied, repetitive allergen challenge(RAC) and diluents were given the allergic patients and health groups for the total 5 doses, two biopsies were taken after 24 hours at the first (Day1) and last challenge (Day11). Immunoreactivity of Activin-A, ALK-4 and TGF-β in the biopsies was assessed by immunohistochemistry and image analysis. ResultsThere were significant higher in the numbers of Activin-A and TGF- β immunoreactive cells at day 11 after repetitive allergen challenge compared to diluents (Median [IQ range]: 43.4 (18.2-69.3) vs. 11.2 (2.9-37.5); p=0.01 for Activin-A, 29.7 (6.6-40.3) vs. 6.6 (1.2-12.3); p=0.04 for TGF-β respectively), the numbers of ALK-4 immunoreactive cells at day 11 were trend to increase compared to diluents (Median [IQ range]: 5.9 (1.3-16.4) vs. 1.4 (0.8-2.9); p=0.06). However, no significant differences in immunoreactivity of these molecules in nasal biopsies were found either between diluents and allergen challenge at day1, or compared with that of the healthy controls. There were significant higher in the numbers of Activin-A and TGF- β immunoreactive cells at day 11 after repetitive allergen challenge compared to diluents (Median [IQ range]: 43.4 (18.2-69.3) vs. 11.2 (2.9-37.5); p=0.01 for Activin-A, 29.7 (6.6-40.3) vs. 6.6 (1.2-12.3); p=0.04 for TGF-β respectively), the numbers of ALK-4 immunoreactive cells at day 11 were trend to increase compared to diluents (Median [IQ range]: 5.9 (1.3-16.4) vs. 1.4 (0.8-2.9); p=0.06). However, no significant differences in immunoreactivity of these molecules in nasal biopsies were found either between diluents and allergen challenge at day1, or compared with that of the healthy controls. ConclusionsOur data suggest that repetitive allergen challenge enhances the expression of activin-A and TGF-β in nasal mucosa of allergic rhinitis. These molecules may contribute to upper airway inflammation and remodelling in allergic rhinitis. Our data suggest that repetitive allergen challenge enhances the expression of activin-A and TGF-β in nasal mucosa of allergic rhinitis. These molecules may contribute to upper airway inflammation and remodelling in allergic rhinitis.