Abstract
Objectives Severe acute pancreatitis is a highly lethal disease caused by systemic inflammatory response syndrome, leading to multiple organ failure. We recently showed that histidine-rich glycoprotein (HRG) supplemental therapy ameliorated septic acute respiratory distress syndrome due to unnecessary neutrophil activation and immunothrombosis formation. Here, we evaluated the effect of HRG on lung inflammation followed by pancreatitis in a severe acute pancreatitis mouse model. Methods Mice received intraperitoneal injections of cerulein 7 times (100 μg/kg each) at 1-hour intervals to induce acute pancreatitis. Immediately after the first cerulein injection, phosphate-buffered saline, human serum albumin (20 mg/kg), or HRG (20 mg/kg) was intravenously injected. One hour after the last cerulein injection, phosphate-buffered saline or lipopolysaccharide (5 mg/kg) was intravenously injected into the tail vein. We evaluated lung inflammatory level after pancreatitis. Results We observed significantly decreased plasma HRG levels in an acute pancreatitis mouse model. Histidine-rich glycoprotein treatment inhibited lung edema and the accumulation of neutrophil in severe acute pancreatitis, but HRG did not directly affect pancreatitis. Moreover, HRG suppressed tumor necrosis factor α, inducible nitric oxide synthase, interleukin 6, and neutrophil elastase mRNA expression and myeloperoxidase activity in the lung. Conclusions These data suggested that HRG ameliorated lung inflammation secondary to pancreatitis.
| Original language | English |
|---|---|
| Pages (from-to) | 1156-1164 |
| Number of pages | 9 |
| Journal | Pancreas |
| Volume | 47 |
| Issue number | 9 |
| DOIs | |
| Publication status | Published - Oct 1 2018 |
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Keywords
- acute respiratory distress syndrome
- histidine-rich glycoprotein
- severe acute pancreatitis
ASJC Scopus subject areas
- Internal Medicine
- Endocrinology, Diabetes and Metabolism
- Hepatology
- Endocrinology
Cite this
Histidine-Rich Glycoprotein Suppresses Hyperinflammatory Responses of Lung in a Severe Acute Pancreatitis Mouse Model. / Terao, Kinya; Wake, Hidenori; Adachi, Naoto; Liu, Keyue; Teshigawara, Kiyoshi; Takahashi, Hideo; Mori, Shuji; Nishibori, Masahiro.
In: Pancreas, Vol. 47, No. 9, 01.10.2018, p. 1156-1164.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Histidine-Rich Glycoprotein Suppresses Hyperinflammatory Responses of Lung in a Severe Acute Pancreatitis Mouse Model
AU - Terao, Kinya
AU - Wake, Hidenori
AU - Adachi, Naoto
AU - Liu, Keyue
AU - Teshigawara, Kiyoshi
AU - Takahashi, Hideo
AU - Mori, Shuji
AU - Nishibori, Masahiro
PY - 2018/10/1
Y1 - 2018/10/1
N2 - Objectives Severe acute pancreatitis is a highly lethal disease caused by systemic inflammatory response syndrome, leading to multiple organ failure. We recently showed that histidine-rich glycoprotein (HRG) supplemental therapy ameliorated septic acute respiratory distress syndrome due to unnecessary neutrophil activation and immunothrombosis formation. Here, we evaluated the effect of HRG on lung inflammation followed by pancreatitis in a severe acute pancreatitis mouse model. Methods Mice received intraperitoneal injections of cerulein 7 times (100 μg/kg each) at 1-hour intervals to induce acute pancreatitis. Immediately after the first cerulein injection, phosphate-buffered saline, human serum albumin (20 mg/kg), or HRG (20 mg/kg) was intravenously injected. One hour after the last cerulein injection, phosphate-buffered saline or lipopolysaccharide (5 mg/kg) was intravenously injected into the tail vein. We evaluated lung inflammatory level after pancreatitis. Results We observed significantly decreased plasma HRG levels in an acute pancreatitis mouse model. Histidine-rich glycoprotein treatment inhibited lung edema and the accumulation of neutrophil in severe acute pancreatitis, but HRG did not directly affect pancreatitis. Moreover, HRG suppressed tumor necrosis factor α, inducible nitric oxide synthase, interleukin 6, and neutrophil elastase mRNA expression and myeloperoxidase activity in the lung. Conclusions These data suggested that HRG ameliorated lung inflammation secondary to pancreatitis.
AB - Objectives Severe acute pancreatitis is a highly lethal disease caused by systemic inflammatory response syndrome, leading to multiple organ failure. We recently showed that histidine-rich glycoprotein (HRG) supplemental therapy ameliorated septic acute respiratory distress syndrome due to unnecessary neutrophil activation and immunothrombosis formation. Here, we evaluated the effect of HRG on lung inflammation followed by pancreatitis in a severe acute pancreatitis mouse model. Methods Mice received intraperitoneal injections of cerulein 7 times (100 μg/kg each) at 1-hour intervals to induce acute pancreatitis. Immediately after the first cerulein injection, phosphate-buffered saline, human serum albumin (20 mg/kg), or HRG (20 mg/kg) was intravenously injected. One hour after the last cerulein injection, phosphate-buffered saline or lipopolysaccharide (5 mg/kg) was intravenously injected into the tail vein. We evaluated lung inflammatory level after pancreatitis. Results We observed significantly decreased plasma HRG levels in an acute pancreatitis mouse model. Histidine-rich glycoprotein treatment inhibited lung edema and the accumulation of neutrophil in severe acute pancreatitis, but HRG did not directly affect pancreatitis. Moreover, HRG suppressed tumor necrosis factor α, inducible nitric oxide synthase, interleukin 6, and neutrophil elastase mRNA expression and myeloperoxidase activity in the lung. Conclusions These data suggested that HRG ameliorated lung inflammation secondary to pancreatitis.
KW - acute respiratory distress syndrome
KW - histidine-rich glycoprotein
KW - severe acute pancreatitis
UR - http://www.scopus.com/inward/record.url?scp=85053696052&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85053696052&partnerID=8YFLogxK
U2 - 10.1097/MPA.0000000000001153
DO - 10.1097/MPA.0000000000001153
M3 - Article
VL - 47
SP - 1156
EP - 1164
JO - Pancreas
JF - Pancreas
SN - 0885-3177
IS - 9
ER -