IRF5 regulates lung macrophages M2 polarization during severe acute pancreatitis in vitro

来源 :World Journal of Gastroenterology | 被引量 : 0次 | 上传用户:chuan9931
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AIM To investigate the role of interferon regulatory factor 5(IRF5) in reversing polarization of lung macrophages during severe acute pancreatitis(SAP) in vitro.METHODS A mouse SAP model was established by intraperitoneal(ip) injections of 20 μg/kg body weight caerulein. Pathological changes in the lung were observed by hematoxylin and eosin staining. Lung macrophages were isolated from bronchoalveolar lavage fluid. The quantity and purity of lung macrophages were detectedby fluorescence-activated cell sorting and evaluated by real-time polymerase chain reaction(RT-PCR). They were treated with IL-4/IRF5 specific siR NA(IRF5 siR NA) to reverse their polarization and were evaluated by detecting markers expression of M1/M2 using RTPCR.RESULTS SAP associated acute lung injury(ALI) was induced successfully by ip injections of caerulein, which was confirmed by histopathology. Lung macrophages expressed high levels of IRF5 as M1 phenotype during the early acute pancreatitis stages. Reduction of IRF5 expression by IRF5 siR NA reversed the action of macrophages from M1 to M2 phenotype in vitro. The expressions of M1 markers, including IRF5(S + IRF5 siR NA vs S + PBS, 0.013 ± 0.01 vs 0.054 ± 0.047, P < 0.01), TNF-α(S + IRF5 siR NA vs S + PBS, 0.0003 ± 0.0002 vs 0.019 ± 0.018, P < 0.001), iN OS(S + IRF5 siR NA vs S + PBS, 0.0003 ± 0.0002 vs 0.026 ± 0.018, P < 0.001) and IL-12(S + IRF5 si RNA vs S + PBS, 0.000005 ± 0.00004 vs 0.024 ± 0.016, P < 0.001), were decreased. In contrast, the expressions of M2 markers, including IL-10(S + IRF5 siR NA vs S + PBS, 0.060 ± 0.055 vs 0.0230 ± 0.018, P < 0.01) and Arg-1(S + IRF5 siR NA vs S + PBS, 0.910 ± 0.788 vs 0.0036 ± 0.0025, P < 0.001), were increased. IRF5 si RNA could reverse the lung macrophage polarization more effectively than IL-4.CONCLUSION Treatment with IRF5 siR NA can reverse the pancreatitisinduced activation of lung macrophages from M1 phenotype to M2 phenotype in SAP associated with ALI. AIM To investigate the role of interferon regulatory factor 5 (IRF5) in reversing polarization of lung macrophages during severe acute pancreatitis (SAP) in vitro. METHODS A mouse SAP model was established by intraperitoneal (ip) injections of 20 μg / kg body weight caerulein . The Pathological changes in the lung were observed by hematoxylin and eosin staining. The quantity and purity of lung macrophages were detected by fluorescence-activated cell sorting and evaluated by real-time polymerase chain reaction (RT-PCR ) They were treated with IL-4 / IRF5 specific siR NA (IRF5 siR NA) to reverse their polarization and were evaluated by detecting markers expression of M1 / ​​M2 using RTPCR.RESULTS SAP associated acute lung injury (ALI) was induced successfully by ip injections of caerulein, which was confirmed by histopathology. Lung macrophages expressed high levels of IRF5 as M1 phenotype during the early acute pancreatitis stages. Reduction of IRF5 expression by IRF5 siR reversed by the action of macrophages from M1 to M2 phenotype in vitro. The expressions of M1 markers, including IRF5 (S + IRF5 siR NA vs. S + PBS, 0.013 ± 0.01 vs 0.054 ± 0.047, P <0.01 (S + IRF5 siR NA vs S + PBS, 0.0003 ± 0.0002 vs. 0.026 ± 0.018, P <0.001) P <0.001) and IL-12 (S + IRF5 si RNA vs. S + PBS, 0.000005 ± 0.00004 vs 0.024 ± 0.016, P <0.001) + IRF5 siR NA vs S + PBS, 0.060 ± 0.055 vs. 0.0230 ± 0.018, P <0.01) and Arg-1 (S + IRF5 siR NA vs S + PBS, 0.910 ± 0.788 vs 0.0036 ± 0.0025, P <0.001) increased. IRF5 si RNA could reverse the lung macrophage polarization more than IL-4.CONCLUSION Treatment with IRF5 siR NA can reverse the pancreatitis induced activation of lung macrophages from M1 phenotype to M2 phenotype in SAP associated with ALI.
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