CircADAMTS-6调控AECOPD细胞模型抗病毒固有免疫的机制研究OA

Objective:To explore the effect of circADAMTS-6 on antiviral innate immune response in cell model of acute ex-acerbation of chronic obstructive pulmonary disease(AECOPD)via regulating miR-1260b/IFNAR2 axis.Methods:(1)Ciga-rette smoke extract(CSE)was used to intervene in BEAS-2B cells to conduct a COPD cell model.The expressions of circAD-AMTS-6,miR-1260b and IFNAR2 were detected by real-time fluorescence quantitative PCR(qRT-PCR),and the IFNAR2 pro-tein expression was detected by Western blot(WB).(2)After overexpression of circADAMTS-6,BEAS-2B cells were treated with CSE combined with viral analogue poly(dA∶dT)to establish an AECOPD cell model.The antiviral innate immune pathway molecules ISG15 and CXCL10 mRNA,as well as STAT1 and STAT2 proteins phosphorylation levels were detected;(3)The relationships among circADAMTS-6,miR-1260b and IFNAR2 were verified via dual-luciferase reporter gene;(4)After overex-pression of IFNAR2 combined with overexpression of miR-1260b or silencing of circADAMTS-6,BEAS-2B cells were inter-vened by CSE plus poly(dA∶dT).Western blots were used to detected the phosphorylation levels of STAT1 and STAT2 pro-teins.Results:(1)The expressions of circADAMTS-6 and IFNAR2 in COPD cell models were decreased,while miR-1260b ex-pression was increased(P<0.05).(2)circADAMTS-6 overexpression promoted ISG15 and CXCL10 mRNA expressions and the STAT1 and STAT2 proteins phosphorylation in AECOPD cell models(P<0.05).(3)miR-1260b interacted with circADAMTS-6 and IFNAR2(P<0.05).(4)IFNAR2 overexpression promoted the STAT1 and STAT2 proteins phosphorylation.Combined overexpression of miR-1260b or silencing circADAMTS-6 reversed the promoting effect of IFNAR2 overexpression(P<0.05).Conclusion:circADAMTS-6 may play a protective role in AECOPD cell model via increasing the IFNAR2 expression by inhibiting miR-1260b,promoting the activation of STAT1/2-mediated antiviral immune pathway.