Protective roles of redox-active protein thioredoxin-1 for severe acute pancreatitis
- 1 April 2006
- journal article
- research article
- Published by American Physiological Society in American Journal of Physiology-Gastrointestinal and Liver Physiology
- Vol. 290 (4), G772-G781
- https://doi.org/10.1152/ajpgi.00425.2005
Abstract
Severe acute pancreatitis is a disease with high mortality, and infiltration of inflammatory cells and reactive oxygen species have a crucial role in the pathophysiology of this disease. Thioredoxin-1 (TRX-1) is an endogenous redox-active multifunctional protein with antioxidant and anti-inflammatory effects. TRX-1 is induced in various inflammatory conditions and shows cytoprotective effects. The aim of the present study was to clarify the protective roles of TRX-1 in the host defense mechanism against severe acute pancreatitis. Experimental acute pancreatitis was induced by intraperitoneal administration of cerulein, a CCK analog, and aggravated by lipopolysaccharide injection in transgenic mice overexpressing human TRX-1 (hTRX-1) and control C57BL/6 mice. Transgenic overexpression of hTRX-1 strikingly attenuated the severity of experimental acute pancreatitis. TRX-1 overexpression suppressed neutrophil infiltration as determined by myeloperoxidase activity, oxidative stress as determined by malondialdehyde concentration, and cytoplasmic degradation of inhibitor of κB-α, thereby suppressing proinflammatory cytokines, tumor necrosis factor-α, interleukin-1β, and interleukin-6; a neutrophil chemoattractant, keratinocyte-derived chemokine; and inducible nitric oxide synthase in the pancreas. Administration of recombinant hTRX-1 also suppressed neutrophil infiltration, reduced the inflammation of the pancreas and the lung, and improved the mortality rate. The present study suggests that TRX-1 has potent antioxidant and anti-inflammatory actions in experimental acute pancreatitis and might be a new therapeutic strategy to improve the prognosis of severe acute pancreatitis.Keywords
This publication has 50 references indexed in Scilit:
- Requirements for the Different Cysteines in the Chemotactic and Desensitizing Activity of Human ThioredoxinAntioxidants and Redox Signaling, 2005
- Treatment with bindarit, a blocker of MCP-1 synthesis, protects mice against acute pancreatitisAmerican Journal of Physiology-Gastrointestinal and Liver Physiology, 2005
- Attenuated Cerulein-Induced Pancreatitis in Nuclear Factor–κB–Deficient MiceLaboratory Investigation, 2003
- Inducible Nitric Oxide Synthase-Deficient Mice Exhibit Resistance to the Acute Pancreatitis Induced by CeruleinShock, 2002
- 1,25-Dihydroxyvitamin D-stimulated calmodulin binding proteins: a sustained effect on distal tubulesAmerican Journal of Physiology-Renal Physiology, 2002
- Antioxidants Inhibit Cytokine Production and Suppress NF-κB Activation in CAPAN-1 and CAPAN-2 Cell LinesDigestive Diseases and Sciences, 2001
- Thioredoxin, a Singlet Oxygen Quencher and Hydroxyl Radical Scavenger: Redox Independent FunctionsBiochemical and Biophysical Research Communications, 2000
- Role of oxidative stress in the pathogenesis of caerulein-induced acute pancreatitisEuropean Journal of Pharmacology, 1999
- Cloning and sequencing of thiol-specific antioxidant from mammalian brain: alkyl hydroperoxide reductase and thiol-specific antioxidant define a large family of antioxidant enzymes.Proceedings of the National Academy of Sciences of the United States of America, 1994
- Measurement of Cutaneous Inflammation: Estimation of Neutrophil Content with an Enzyme MarkerJournal of Investigative Dermatology, 1982