A Study Of RSV-TLR3-mediated Immune Response And The Pathogenesis Of AECOPD

【Objective】To explore TLR3is role in the COPD by exploring RSV, TLR3expression in theAECOPD patients, revealing virus-mediated immune and inflammatory response may beinvolved in the pathogenesis of COPD3. Further explore TLR3signaling pathway in thelung epithelial cells.【Methods】TLR3mRNA were detected in sputum with AECOPD (20cases) patients and normalcontrol subjects (10cases) By Real-Time PCR, RSV were detected in sputum withAECOPD patients by trough PCR; Clinical data of patients with AECOPD were Collected,including the basic characteristics of the patient, blood, blood gas, lung function, IL-6, PCT.And it was statistically analyzed. Pearson correlation analysis applied to analyze therelevance of TLR3with COPD. The A549cells were by RSV infection in6,12,18,24,36different time and100TCID50,500TCID50,1000TCID50different viral titer, RT-PCRdetection TLR3mRNA expression, Western Blot to detect the protein expression of TLR3and IRF3, IRF3protein localization by immunofluorescence. INF-β and IL-6weredetected in cell supernatants by ELISA.【Results】RSV was detected in4(20%) cases in20cases of AECOPD group of patients.FEV1%, FEV1/FVC lower in was detected RSV of AECOPD than was not detected RSVof AECOPD Respectively（P=0.03,0.01respectively），IL-6is higher in was detectedRSV of AECOPD than was not detected RSV of AECOPD（P=0.04）. The AECOPD group(n=20) showed a increase in TLR3mRNA compared with TLR3mRNA in the control（n=10），The difference in TLR3mRNA Increase between these two groups wassignificant (P=0.02). The RSV were dected AECOPD group (n=4) showed a increase inTLR3mRNA compared with the RSV were not dected AECOPD group TLR3mRNA(P=0.33) and showed a increase obviously compared with TLR3mRNA in the control （n=10）(P=0.03). TLR3mRNA increases in sputum associated with FEV1%rating toreduce the severity of AECOPD in20AECOPD patient（sP=0.031r=-0.482）. TLR3mRNA/protein increases compared with the control group in A549with RSV infctiion. TLR3signaling factors downstream IRF3protein also increases and the occurrence of nucleartransfer in A549with RSV infctiion. IRF3mediated production INF-β and TLR3-NF-kbsignaling pathway mediated production IL-6both increase compared with INF-βand IL-6in the control in RSV infected A549cells (P=0.00,0.00respectively).【Conelusions】TLR3increases associated with FEV1%rating to reduce the severity of AECOPDpatients. TLR3produce large amounts of inflammatory cytokines when it antiviral activityin the A549lung epithelial cells with RSV infection, suggesting TLR3may a pathogenicrole when it antiviral simultaneously. TLR3increases compared with the control group inAECOPD patients with RSV infection, suggesting that RSV may be an importantpathogenic factor in AECOPD and TLR3-induced immune response may be involved inthe pathogenesis of COPD...