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Downregulation of HMGB1 protects against the development of acute lung injury after severe acute pancreatitis.

Authors: Luan, ZG  Zhang, XJ  Yin, XH  Ma, XC  Zhang, H  Zhang, C  Guo, RX 
Citation: Luan ZG, etal., Immunobiology. 2013 Oct;218(10):1261-70. doi: 10.1016/j.imbio.2013.04.013. Epub 2013 Apr 28.
Pubmed: (View Article at PubMed) PMID:23706497
DOI: Full-text: DOI:10.1016/j.imbio.2013.04.013

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-alpha (TNF-alpha) and interleukin-1beta (IL-1beta) 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-kappaB) 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-kappaB, thus aggratating the severity of SAP associated with ALI.


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RGD Object Information
RGD ID: 10402063
Created: 2015-10-14
Species: All species
Last Modified: 2015-10-14
Status: ACTIVE


RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.