title: IRF5 regulates lung macrophages M2 polarization during severe acute pancreatitisin vitro.
abstract: OBJECTIVE
  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 detected by fluorescence-activated cell sorting and evaluated by real-time polymerase chain reaction (RT-PCR). They were treated with IL-4/IRF5 specific siRNA (IRF5 siRNA) to reverse their polarization and were evaluated by detecting markers expression of M1/M2 using RT-PCR.
  
  
  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 siRNA reversed the action of macrophages from M1 to M2 phenotypein vitro. The expressions of M1 markers, including IRF5 (S + IRF5 siRNAvsS + PBS, 0.013 ± 0.01vs0.054 ± 0.047,P< 0.01), TNF-α (S + IRF5 siRNAvsS + PBS, 0.0003 ± 0.0002vs0.019 ± 0.018,P< 0.001), iNOS (S + IRF5 siRNAvsS + PBS, 0.0003 ± 0.0002vs0.026 ± 0.018,P< 0.001) and IL-12 (S + IRF5 siRNAvsS + PBS, 0.000005 ± 0.00004vs0.024 ± 0.016,P< 0.001), were decreased. In contrast, the expressions of M2 markers, including IL-10 (S + IRF5 siRNAvsS + PBS, 0.060 ± 0.055vs0.0230 ± 0.018,P< 0.01) and Arg-1 (S + IRF5 siRNAvsS + PBS, 0.910 ± 0.788vs0.0036 ± 0.0025,P< 0.001), were increased. IRF5 siRNA could reverse the lung macrophage polarization more effectively than IL-4.
  
  
  CONCLUSIONS
  Treatment with IRF5 siRNA can reverse the pancreatitis-induced activation of lung macrophages from M1 phenotype to M2 phenotype in SAP associated with ALI.
authors.affiliation: Kang Sun, Jian-Guo Qu, Sheng-Chun Dang, Ji-Xiang Chen, Rong Xie, Jian-Xin Zhang, Department of General Surgery, The Affiliated Hospital of Jiangsu University, Zhenjiang 212001, Jiangsu Province, China.
authors.forename: Kang
authors.initials: K
authors.lastname: Sun
authors.affiliation: Kang Sun, Jian-Guo Qu, Sheng-Chun Dang, Ji-Xiang Chen, Rong Xie, Jian-Xin Zhang, Department of General Surgery, The Affiliated Hospital of Jiangsu University, Zhenjiang 212001, Jiangsu Province, China.
authors.forename: Song-Bing
authors.initials: SB
authors.lastname: He
authors.affiliation: Kang Sun, Jian-Guo Qu, Sheng-Chun Dang, Ji-Xiang Chen, Rong Xie, Jian-Xin Zhang, Department of General Surgery, The Affiliated Hospital of Jiangsu University, Zhenjiang 212001, Jiangsu Province, China.
authors.forename: Jian-Guo
authors.initials: JG
authors.lastname: Qu
authors.affiliation: Kang Sun, Jian-Guo Qu, Sheng-Chun Dang, Ji-Xiang Chen, Rong Xie, Jian-Xin Zhang, Department of General Surgery, The Affiliated Hospital of Jiangsu University, Zhenjiang 212001, Jiangsu Province, China.
authors.forename: Sheng-Chun
authors.initials: SC
authors.lastname: Dang
authors.affiliation: Kang Sun, Jian-Guo Qu, Sheng-Chun Dang, Ji-Xiang Chen, Rong Xie, Jian-Xin Zhang, Department of General Surgery, The Affiliated Hospital of Jiangsu University, Zhenjiang 212001, Jiangsu Province, China.
authors.forename: Ji-Xiang
authors.initials: JX
authors.lastname: Chen
authors.affiliation: Kang Sun, Jian-Guo Qu, Sheng-Chun Dang, Ji-Xiang Chen, Rong Xie, Jian-Xin Zhang, Department of General Surgery, The Affiliated Hospital of Jiangsu University, Zhenjiang 212001, Jiangsu Province, China.
authors.forename: Ai-Hua
authors.initials: AH
authors.lastname: Gong
authors.affiliation: Kang Sun, Jian-Guo Qu, Sheng-Chun Dang, Ji-Xiang Chen, Rong Xie, Jian-Xin Zhang, Department of General Surgery, The Affiliated Hospital of Jiangsu University, Zhenjiang 212001, Jiangsu Province, China.
authors.forename: Rong
authors.initials: R
authors.lastname: Xie
authors.affiliation: Kang Sun, Jian-Guo Qu, Sheng-Chun Dang, Ji-Xiang Chen, Rong Xie, Jian-Xin Zhang, Department of General Surgery, The Affiliated Hospital of Jiangsu University, Zhenjiang 212001, Jiangsu Province, China.
authors.forename: Jian-Xin
authors.initials: JX
authors.lastname: Zhang
mesh_terms: D055371:Acute Lung Injury / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D002478:Cells, Cultured; D002108:Ceruletide; D004195:Disease Models, Animal; D005260:Female; D050835:Interferon Regulatory Factors / Q000235:genetics / Q000378:metabolism*; D008262:Macrophage Activation; D016676:Macrophages, Alveolar / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008810:Mice, Inbred C57BL; D010195:Pancreatitis / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D010641:Phenotype; D034622:RNA Interference; D012720:Severity of Illness Index; D015398:Signal Transduction; D013997:Time Factors; D014162:Transfection
chemical_list: D050835:Interferon Regulatory Factors; C498178:Irf5 protein, mouse; D002108:Ceruletide
keywords: Interferon regulatory factor 5; Macrophage polarization; Severe acute pancreatitis; SiRNA