title: Downregulation of HMGB1 protects against the development of acute lung injury after severe acute pancreatitis.
abstract: OBJECTIVE
  To examine the effect of downregulation of high mobility group box 1 (HMGB1) on severe acute pancreatitis (SAP) associated with acute lung injury (ALI), and its subsequent effect on disease severity.
  
  
  METHODS
  Wistar rats were given an IV injection of pRNA-U6.1/Neo-HMGB1, pRNA-U6.1/Neo-vector or saline before induction of SAP. Then, SAP was induced in rats by the retrograde injection of 5% sodium taurocholate into the pancreatic duct. The control group received only a sham operation. Lung and pancreas samples were harvested after induction of SAP. The protein levels of HMGB1, matrix metalloproteinase-9 (MMP-9) and intercellular adhesion molecule-1 (ICAM-1) in lung tissue were investigated. The severity of pancreatic injury was determined by a histological score of pancreatic injury, serum amylase, and pancreatic water content. The lung injury was evaluated by measurement of pulmonary microvascular permeability, lung myeloperoxidase activity and malondialdehyde levels.
  
  
  RESULTS
  The results found that in pRNA-U6.1/Neo-HMGB1 treated rats, serum tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) levels were decreased and the severity of pancreatic tissue injury was less compared with either untreated SAP or pRNA-U6.1/Neo-vector treated rats (P<0.05). The administration of pRNA-U6.1/Neo-HMGB1 in SAP-induced rats downregulated the DNA binding activity of the nuclear factor-kappa B (NF-κB) and the expressions of MMP-9 and ICAM-1 in lung. Thus, compared with the untreated SAP rats, the inflammatory response and the severity of ALI decreased (P<0.05).
  
  
  CONCLUSIONS
  These results demonstrate that HMGB1 could augment Inflammation by inducing nuclear translocation of NF-κB, thus aggratating the severity of SAP associated with ALI.
authors.affiliation: Department of Intensive Care Unit, The First Hospital, China Medical University, Shenyang, China. zgl17698@sina.com
authors.forename: Zheng-Gang
authors.initials: ZG
authors.lastname: Luan
authors.forename: Xiao-Juan
authors.initials: XJ
authors.lastname: Zhang
authors.forename: Xiao-Han
authors.initials: XH
authors.lastname: Yin
authors.forename: Xiao-Chun
authors.initials: XC
authors.lastname: Ma
authors.forename: Hao
authors.initials: H
authors.lastname: Zhang
authors.forename: Cheng
authors.initials: C
authors.lastname: Zhang
authors.forename: Ren-Xuan
authors.initials: RX
authors.lastname: Guo
mesh_terms: D055371:Acute Lung Injury / Q000209:etiology / Q000276:immunology* / Q000517:prevention & control; D000818:Animals; D018450:Disease Progression; D015536:Down-Regulation; D024243:HMGB1 Protein / Q000235:genetics / Q000378:metabolism*; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism; D053583:Interleukin-1beta / Q000097:blood; D008168:Lung / Q000378:metabolism*; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism*; D019283:Pancreatitis, Acute Necrotizing / Q000150:complications / Q000276:immunology* / Q000628:therapy; D011485:Protein Binding / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D013656:Taurocholic Acid / Q000008:administration & dosage; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: D024243:HMGB1 Protein; C573420:ICAM1 protein, human; D053583:Interleukin-1beta; D016328:NF-kappa B; D034741:RNA, Small Interfering; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1; D013656:Taurocholic Acid; D020780:Matrix Metalloproteinase 9
keywords: ALI; ELISA; EMSA; HMGB1; High mobility group box 1; ICAM-1; IL-1β; Inflammation; Lung injury; MDA; MMP-9; MPO; NF-κB; SAP; Severe acute pancreatitis; TNF-α; acute lung injury; electrophoretic mobility shift assay; enzyme-linked immunosorbent assay; high mobility group box 1; intercellular adhesion molecule-1; interleukin-1β; malondialdehyde; matrix metalloproteinase-9; myeloperoxidase; nuclear factor-kappa B; severe acute pancreatitis; tumor necrosis factor-α