1. Heme oxygenase-1 induced by desoxo-narchinol-A attenuated the severity of acute pancreatitis via blockade of neutrophil infiltration.
- Author
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Bae GS, Kim DG, Jo IJ, Choi SB, Kim MJ, Shin JY, Kim DU, Song HJ, Joo M, and Park SJ
- Subjects
- Acute Disease, Amylases blood, Animals, Ceruletide administration & dosage, Cytokines metabolism, Disease Models, Animal, Female, Humans, Inflammation Mediators metabolism, Mice, Mice, Inbred C57BL, Naphthols metabolism, Neutrophil Infiltration, Pancreas pathology, Pancreatitis pathology, Chemokine CXCL2 metabolism, Heme Oxygenase-1 metabolism, Neutrophils physiology, Pancreas metabolism, Pancreatitis metabolism
- Abstract
Heme oxygenase-1 (HO-1) has an anti-inflammatory action in acute pancreatitis (AP). However, its mechanism of action and natural compounds/drugs to induce HO-1 in pancreas are not well understood. In this study, we investigated the regulatory mechanisms of HO-1 during AP using desoxo-narchinol-A (DN), the natural compound inducing HO-1 in the pancreas. Female C57/BL6 Mice were intraperitoneally injected with supramaximal concentrations of cerulein (50 μg/kg) hourly for 6 h to induce AP. DMSO or DN was administered intraperitoneally, then mice were sacrificed 6 h after the final cerulein injection. Administration of DN increased pancreatic HO-1 expression through activation of activating protein-1, mediated by mitogen-activated protein kinases. Furthermore, DN treatment reduced the pancreatic weight-to-body weight ratio as well as production of digestive enzymes and pro-inflammatory cytokines. Inhibition of HO-1 by tin protoporphyrin IX abolished the protective effects of DN on pancreatic damage. Additionally, DN treatment inhibited neutrophil infiltration into the pancreas via regulation of chemokine (C-X-C motif) ligand 2 (CXCL2) by HO-1. Our results suggest that DN is an effective inducer of HO-1 in the pancreas, and that HO-1 regulates neutrophil infiltration in AP via CXCL2 inhibition., (Copyright © 2019 Elsevier B.V. All rights reserved.)
- Published
- 2019
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