The proinflammatory role of SOCS3 in COPD is regulated by the expression of miRNAs in Bronchoalveolar Lavage (BAL) microvesicles (MV)

Introduction: Originally described as an anti-inflammatory in vitro, the Suppressor of Cytokine Signalling (SOCS) proteins seem to have an opposite effect in vivo. Along with this possibility we have previously observed a higher expression of SOCS3 in alveolar macrophages (AM) in COPD lungs than in healthy smoker and nonsmoker lungs. Aim: To investigate: 1) if AM-derived MV in BAL could reflect SOCS3 expression in lung AM; and 2) if SOCS3 expression in AM is regulated by the SOCS3 post-transcriptional regulators, miR-19a-3p and miR-221-3p in MV. Methods: BAL from 5 nonsmokers (NS), 11 smokers w/o COPD (S) and 9 smokers with COPD was collected. Differential centrifugation of BAL was performed and the final sample divided in 2 aliquots to: 1) isolate and detect by flow cytometry MV of AM origin expressing SOCS3 (CD14+SOCS3+); 2) analyse and quantify by quantitative PCR the differential expression of miR-19a-3p and miR-221-3p in AM-derived MV. Results: CD14+SOCS3+ expression in MV from BAL was increased in COPD compared to NS [33(26-97) vs 9(8-17) events/?l p=0.003] and to S [16(12-22) p=0.03]. Conversely the expression in BAL MV of the SOCS3 regulators miR-19a-3p and miR-221-3p was increased in S when compared to COPD [19(2-53) vs 3(0.6-8) p=0.03 and 3(0.005-9.6) vs 0.2(0.08-0.7) p=0.06, respectively]. Conclusions: BAL-derived MV are able to reflect the differential expression of SOCS3 in lung AM of smokers with and w/o COPD. Furthermore, with the use of MV we showed that SOCS3 expression in COPD is enhanced by the decreased expression of regulatory miRNAs. These results underline the role of MV as a tool for the study of lung events.