The Role Of IL-17A Induced Epithelial-mesenchymal Transition In CRSwNP Through NLRP3 Activation

Objective: To investigate the function of IL-17 A in TGF-β1-mediated epithelialmesenchymal transition(EMT)through activating NLRP3 inflammasome in chronic rhinosinusitis with nasal polyps(CRSw NP).Methods:1、The expression of IL-17 A,NLRP3,TGF-β1 and EMT-related genes(Ecadherin,vimentin,α-SMA)in CRSw NP group and normal controls were detected by q RT-PCR,IHC and WB.2、A different concentration of IL-17A(0,100,200,300,and 500 ng/m L)was used to stimulate the human nasal epithelial cells(HNEp Cs).After 48 hours of stimulation,the expression of E-cadherin,vimentin,α-SMA,NLRP3,and TGF-β1 was determined by q RT-PCR and WB.3、After pretreated with HY10431,a selective inhibitor of TGF-β1,HNEp Cs were stimulated with IL-17 A.Afterward,q RT-PCR and WB were used to evaluate the expression of NLRP3 and EMT-related genes.4、 Before stimulated with IL-17 A,HNEp Cs were pretreated with CY-09,a specific inhibitor of NLRP3.Then the expression of NLRP3,TGF-β1 and EMT-related genes was examined using q RT-PCR and WB.Results:1、According to the result of IHC,the expression levels of TGF-β1,NLRP3,vimentin,and α-SMA were increased and E-cadherin was diminished in CRSw NP compared with the control(P < 0.05).2、q RT-PCR and WB showed the higher expression of TGF-β1,NLRP3,vimentin,and α-SMA in patients with CRSw NP than that in normal controls,while E-cadherin expression was lower(P < 0.05).3、After stimulation of IL-17 A in nasal epithelial cells,the NLRP3,TGF-β1,vimentin,and α-SMA expressed more in both m RNA and protein level,while Ecadherin expressed less(P < 0.05);4、Compared with IL-17 A group,the expression level of vimentin and α-SMA were dropped,and expression of E-cadherin was raised(P < 0.05,respectively),while NLRP3 expression was not significantly changed(P>0.05)in the IL-17A+HY10431group.5、When compared to IL-17 A group,the expression levels of NLRP3,TGF-β1,vimentin,and α-SMA were diminished,while E-cadherin expression was augmented(P < 0.05,respectively)in the IL-17A+ CY-09 group.Conclusion: IL-17 A can induce the TGF-β1 pathway-mediated EMT through activating NLRP3 in CRSw NP.