Expression of oxidative stress-responsive genes and cytokine genes during caerulein-induced acute pancreatitis

Am J Physiol. 1997 Sep;273(3 Pt 1):G696-705. doi: 10.1152/ajpgi.1997.273.3.G696.


Oxidative stress and the inflammatory response may play roles in the pathogenesis of acute pancreatitis. Herein, we characterized pancreatic expression of oxidative stress-responsive genes [c-fos, heme oxygenase-1 (HO-1), and metallothionein-I (MT-I)] and cytokine genes [interleukin-1 beta (IL-1 beta), IL-6, and tumor necrosis factor-alpha (TNF-alpha)] during caerulein-induced acute pancreatitis in the mouse. c-fos, HO-1, and MT-I mRNAs were coordinately and rapidly (3-7 h) upregulated, and HO-1 and MT-I protein levels were increased slightly in the pancreas during acute pancreatitis. In addition, IL-1 beta, IL-6, and TNF-alpha mRNAs were rapidly (7 h) upregulated in the pancreas, and intrapancreatic IL-1 beta and IL-6 protein levels rapidly increased (3-fold and 6.4-fold, respectively) during acute pancreatitis. These studies suggest that oxidative stress and inflammation each occur in the pancreas during the early stages of acute pancreatitis. However, under a limited set of experimental conditions, we found that an insult that causes pancreatic oxidative stress (diethylmaleate) or one that induces an inflammatory response (bacterial lipopolysaccharide), or a combination of these agents, did not cause the changes characteristic of acute pancreatitis. Therefore, simply inducing oxidative stress and/or inflammation may be insufficient to initiate acute pancreatitis.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Acute Disease
  • Animals
  • Ceruletide
  • Cloning, Molecular
  • Cytokines / biosynthesis*
  • Escherichia coli
  • Genes, fos
  • Glutathione / metabolism
  • Heme Oxygenase (Decyclizing) / biosynthesis*
  • Heme Oxygenase-1
  • Interleukin-1 / biosynthesis
  • Interleukin-6 / biosynthesis
  • Lipopolysaccharides / pharmacology
  • Male
  • Membrane Proteins
  • Metallothionein / biosynthesis*
  • Mice
  • Mice, Inbred Strains
  • Oxidative Stress*
  • Pancreas / drug effects
  • Pancreas / metabolism*
  • Pancreas / pathology
  • Pancreatitis / chemically induced
  • Pancreatitis / metabolism*
  • Pancreatitis / pathology
  • Proto-Oncogene Proteins c-fos / biosynthesis*
  • RNA, Messenger / biosynthesis
  • Transcription, Genetic* / drug effects
  • Tumor Necrosis Factor-alpha / biosynthesis
  • alpha-Amylases / biosynthesis


  • Cytokines
  • Interleukin-1
  • Interleukin-6
  • Lipopolysaccharides
  • Membrane Proteins
  • Proto-Oncogene Proteins c-fos
  • RNA, Messenger
  • Tumor Necrosis Factor-alpha
  • Ceruletide
  • Metallothionein
  • Heme Oxygenase (Decyclizing)
  • Heme Oxygenase-1
  • Hmox1 protein, mouse
  • alpha-Amylases
  • Glutathione