Effects of benzo(a)pyrene on nasal mucosa function and methylation level of Treg cells in allergic rhinitis(AR)model
Objective To investigate the effects of benzo(a)pyrene on nasal mucosa function and methyla-tion level of Treg cells in models of allergic rhinitis(AR).Methods 12 of 36 SPF-grade BALB/c female mice were selected as normal control group,and the remaining mice were randomly divided into AR model group and the benzo(a)pyrene intervention group using a random number table,with 12 mice in each group.The AR model group and the benzo(a)pyrene intervention group were subjected to modeling treat-ment.After the modeling,the benzo(a)pyrene intervention group was injected with 7.89 mg/kg body weight of benzo(a)pyrene.The control group and AR model group were given the same amount of sterile PBS solution intraperitoneal injection.The scores of rhinitis symptoms,EOS count in nasal perfusion flu-id,serum levels of OVA-sIgE,GM-CSF,TNF-α,IL-13 and Eotaxin,pathological changes of mouse nasal mucosa,Th subgroup of mouse nasal mucosa and Foxp3 methylation and protein levels were compared in each group.Results Compared with AR model group,the rhinitis symptom score and EOS count of nasal lavage fluid were significantly increased in the benzo(a)pyrene intervention group(P＜0.05),and the serum levels of OVA-sIgE,GM-CSF,TNF-α,IL-13 and Eotaxin were significantly increased(P＜0.05).After intervention of benzo(a)pyrene,a large number of inflammatory cells were infiltrated,the nasal epithelium was disordered,hyperplasia and vasodilation were serious,the fibrous epithelium was also seri-ously damaged,and a large number of goblet cells appeared.The number of AhR positive cells in the nasal mucosa of benzo(a)pyrene intervention group was the most significantly increased(P＜0.05).The pro-portion of Th1 and Treg were decreased significantly,and the proportion of Th2 and Th17 were increased significantly(P＜0.05)in the benzo(a)pyrene intervention group.The methylation level of Foxp3 gene in CD4+CD25+regulatory T cells in mouse spleen was increased significantly(P＜0.05),and the Foxp3 protein level in mouse spleen was decreased significantly(P＜0.05)in the benzo(a)pyrene intervention group.Conclusion Benzo(a)pyrene may aggravate nasal mucosal inflammation and immune imbalance,promote abnormal differentiation of Treg cells and Foxp3 gene methylation of CD4+CD25-regulatory T cells,and then participate in the pathogenesis of allergic rhinitis.
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