Ralatiomship Between Oncostatin M And Tijht Junctions Dysfunction,and Its Expression In Humam Nasal Epithelial Cells Infected With H3N2 Influenza Virus

Objective:To investigate OSM expression and TJs alterations in CRSwNP,and the effects of influenza A virus(IAV)on inducing OSM expression in the nasal epithelium.Methods:1、The expression of OSM and TJs were measured by using Quantitative Real-Time Polymerase Chain Reaction(qPCR)and immunofluorescence(IF)staining,and was compared between inferior turbinate from healthy subjects(controls)and nasal polyps from chronic rhinosinusitis with nasal polyps(CRSwNP)patients.2、To detect the expression of OSM in human nasal epithelial cells(hNECs)cultured at the air-liquid interface were infected with H3N2 influenza virus,To detect the expression of OSM was assessed by using qPCR and double IF staining with viral hemagglutinin(HA1)and markers of various cell types.OSM was assessed by using double IF staining with viral hemagglutinin(HA1)and markers of various cell types.Results:1、ZO-1 and claudin-1 mRNA levels were significantly decreased in CRSwNP(p<0.001 and p<0.001)compared to control subjects;while occludin showed no differences in mRNA expression levels.OSM mRNA expression was increased in patients with CRSwNP(P<0.05).Furthermore,OSM levels in nasal polyp tissues and negatively correlated with levels of ZO-1(r=-0.381;P=0.015),claudin-1(r=-0.476;P=0.002)and occludin(r=-0.382;P=0.015).2、In vitro cultured hNECs could express high levels of OSM with H3N2infection in all 11 subjects,which increased logarithmic and peaked at 24 hpi(p<0.05)and more than 4.6 fold increase vs mock infection control(median,2.2,4.7 and 3.9fold increase vs mock infection control,respectively at 8,24,and 48 hpi)By using double immunofluorescence,we showed that some colocalization with a minor population of HA1 on 24hpi and 48hpi.Quantification of TFI showed a trend toward higher intensity of OSM in H3N2-infected hNECs(0.033×10~7,0.144×10~7,2.99×10~7and 2.94×10~7).Using double-IF we observed OSM colocalization with ciliated and goblet cells in hNECs infected with H3N2 influenza virus and did not observe colocalization of OSM with markers for basal cells.Conclusions:1、The expression of TJs in nasal polyps were decreased and negatively correlated with the expression of OSM.2、H3N2 influenza virus causes high expression of OSM in hNECs and may be disturb the epithelial TJs.Ciliated cells and goblet cells in nasal epithelial cells may be an important source of OSM.