Histidine-Rich Glycoprotein Suppresses Hyperinflammatory Responses of Lung in a Severe Acute Pancreatitis Mouse Model

Kinya Terao, Hidenori Wake, Naoto Adachi, Keyue Liu, Kiyoshi Teshigawara, Hideo Takahashi, Shuji Mori, Masahiro Nishibori

Research output: Contribution to journalArticle

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 languageEnglish
Pages (from-to)1156-1164
Number of pages9
JournalPancreas
Volume47
Issue number9
DOIs
Publication statusPublished - Oct 1 2018

Fingerprint

Pancreatitis
Lung
Ceruletide
Pneumonia
Phosphates
histidine-rich proteins
Systemic Inflammatory Response Syndrome
Neutrophil Activation
Leukocyte Elastase
Injections
Multiple Organ Failure
Adult Respiratory Distress Syndrome
Nitric Oxide Synthase Type II
Intraperitoneal Injections
Serum Albumin
Peroxidase
Lipopolysaccharides
Tail
Veins
Interleukin-6

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 journalArticle

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