Environmental Pollutant MNP Promotes Allergic Rhinitis By Regulating The Activity Of Nasal Mucosa

Background:Allergic rhinitis is a common disease in otolaryngology,affecting about 10%40%of the global population.The main pathological mechanism of allergic rhinitis is IgE-mediated type I allergy.As an important channel connecting the external environment and the internal environment,the nasal cavity’s own tissue microenvironment plays an important role in buffering the balance between the two.When allergic rhinitis occurs,the role of environmental pollutants in it is not clear.Therefore,our experiment aims to explore the relationship between environmental pollutants and allergic rhinitis.Purpose:The mouse model of allergic rhinitis was established by using ovalbumin(OVA)and environmental pollutant 3-methyl-4-nitrophenol(MNP)to explore whether the environmental pollutant MNP can aggravate the symptoms of allergic rhinitis and explore its possible mechanism,so as to provide theoretical basis and potential solution for the future treatment of allergic rhinitis.Methods:(1)The mouse model of allergic rhinitis aggravated by MNP was established,and the behavioral indexes of mice were recorded,the serum specific IgE and IgG1 were detected,the inflammatory changes of nasal mucosa and lung tissue were observed,the levels of related inflammatory factors in nasal lavage fluid and bronchoalveolar lavage fluid and the proportion of spleen Th2 cells were detected.(2)The apoptosis-promoting effect of MNP on nasal mucosal epithelial cells was observed,the content of extracellular DNA in the supernatant was detected,and the inducing effect of extracellular DNA on CD4+T cells was verified by cell experiment.(3)To observe the relieving effect of intranasal instillation of DNA enzyme on mice with allergic rhinitis aggravated by MNP and compare with the mouse model of allergic rhinitis aggravated by MNP to evaluate its relieving effect.Results:(1)Compared with the allergic rhinitis mouse model without MNP treatment,the allergic rhinitis mouse model treated with MNP increased the number of sneezing and scratching,the level of serum OVA specific antibody IgE and IgG1,the Th2 type cytokines in nasal cavity and bronchoalveolar lavage fluid,the inflammation of nasal cavity and lung tissue and the proportion of Th2 in spleen cells.The above results suggest that MNP can aggravate the symptoms of allergic rhinitis in mice.(2)MNP intranasally induced apoptosis of mouse nasal mucosal epithelial cells,and the content of extracellular DNA in the supernatant increased with the increase of apoptotic cells,and this change was related to the concentration of MNP.Extracellular DNA can induce the expression of IL-4,IL-5 and IL-13 in primary CD4+T cells of mouse spleen,which may be related to TLR9.It can also induce the expression of Th2-related cytokines and TLR9 in EL-4 and Jurkat cell lines.(3)Blocking extracellular DNA can alleviate the clinical manifestations of allergic rhinitis induced by MNP,reduce the levels of OVA specific antibodies IgE and IgG1 in serum,reduce the severity of histopathology,and reduce the proportion of Th2 cytokines in nasal cavity and bronchoalveolar lavage fluid and the proportion of Th2 in spleen cells and lung tissue.Conclusion:The environmental pollutant 3-methyl-4-nitrophenol can aggravate allergic rhinitis,It’s mechanism may be the 3-methyl-4-nirophenol can inducing nasal mucosal epithelial cell apoptosis,apoptotic cells release extracellular DNA,extracellular DNA may interact with TLR9 in CD4+T cell,thus inducing CD4+T cells to Th2 differentiation,then aggravating Th1/Th2 bias of the body,thus aggravating the symptoms of allergic rhinitis.