Relationship Between IL-17C,notch And MAPK/NF-кB Signaling Pathway In Chronic Sinusitis With Nasal Polyps

Objective:To explore the mechanism of IL-17C in chronic sinusitis with nasal polyps and the role of Notch signal transduction in the pathogenesis of chronic sinusitis with nasal polyps.Methods:1.From September 2019 to December 2019,10 adult chronic sinusitis patients with nasal polyps and 5 patients with deviation of nasal septum were recruited.The expression of IL-17C in the two groups was detected by Real-Time PCR.2.Fifteen 7-week-old BALE/c mice were randomly divided into three groups,five in each group:control group,OVA group,OVA+γ-secretase inhibitor group.Mice were sensitized by intraperitoneal injection of 0.1ml containing Aluminium Hydroxide Gel 2mg phosphate buffer solution or 0.1ml containing 25μg OVA and 2mg Aluminium Hydroxide Gel saline on zeroth and seventh days.After general sensitization,mice were stimulated intranasal with 40μl PBS or 6%OVA from the 14th to the 20th day.After that,40 μl PBS or 6%OVA were used to stimulate the mice in the nose three times a week for two weeks.After 8 weeks,the OVA group was induced by 6%Staphylococcus aureus enterotoxin b1Ong at the same time,and perfused the nasal cavity of mice three times a week.In the OVA+GSI group,GSI was given to the nose 30 minutes before each OVA stimulation at a dose of 0.3 mg/kg.The mice in the negative control group did not receive OVA,SEB and GSI.After the mice were anesthetized and killed,the nasal mucosa was completely removed and he staining was performed to confirm whether there was inflammatory infiltration in the nasal mucosa.3.The expression of IL-17C in human polyp group,human control group,mouse control group,mouse OVA group and mouse OVA+GSI group was detected by immunohistochemistry.4.The toxicity of IL-17C at different concentrations on human nasal polyp fibroblasts was detected by MTS.5.The expression levels of p-ERK,p-JNK,p-p38 and p-IκBα were detected by Western blot without the presence of mitogen activated kinase(MAPK)/nuclear factor(NF)-κB signal transduction pathway specific inhibitors.Results:1.The results of immunohistochemistry showed that the percentage of IL-17C positive cells in the polyp group was significantly higher than that in the control group(P<0.001),and the Real-Time PCR showed that the expression of IL-17C in the polyp group was significantly higher than that in the control group(P<0.001).2.HE staining showed that eosinophils increased significantly in OVA group,while pathological changes in OVA+GSI group were less than those in ova group.There was no obvious pathological change in the normal group.3.The results of immunohistochemical staining showed that the expression of IL-17C was not significant in the control group,and the expression of IL-17C was high in the OVA group,and the difference was statistically significant(P<0.05).The expression of IL-17C in the OVA+GSI group was significantly lower than that in the OVA group,and the difference was statistically significant(P<0.05).4.MTS results showed that IL-17C of different concentrations(5,10,25,50,100,200ng/ml)had no toxic effect on the fibroblasts of nasal polyps compared with the control group.5.Western blotting results showed that the expression of p-ERK,p-JNK,p-p38,p-IκBα protein in the IL-17C group was significantly higher than that in the control group p-ERK,p-JNK,p-p38,p-IκBα protein in the IL-17C group was significantly lower than that in the control group(P<0.001).Conclusions:1.IL-17C is involved in the pathogenesis of chronic sinusitis with nasal polyps.During the pathogenesis,it induces inflammation through MAPK/NF-κB signal transduction pathway.2.By inhibiting Notch signaling,IL-17C in the nasal mucosa of mice can be down regulated,thus reducing the inflammatory response of the nasal mucosa of mice.