Over-expression of pancreatic pituitary adenylate cyclase-activating polypeptide (PACAP) aggravates cerulein-induced acute pancreatitis in mice
| Autor: | Norihito Shintani, Hiroshi Kiyama, Hitoshi Hashimoto, Kazuya Ikeda, Ken-ichi Hamagami, Yusuke Sakurai, Naoko Higuchi, Akemichi Baba, Akinobu Suzuki |
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| Rok vydání: | 2009 |
| Předmět: |
Genetically modified mouse
medicine.medical_specialty endocrine system Necrosis Down-Regulation Inflammation Mice Transgenic Pancreatitis-Associated Proteins Proinflammatory cytokine Mice Internal medicine Insulin-Secreting Cells medicine Animals RNA Messenger Pharmacology business.industry lcsh:RM1-950 Proteins Lipase medicine.disease Up-Regulation Disease Models Animal Endocrinology medicine.anatomical_structure lcsh:Therapeutics. Pharmacology Pancreatitis Acute Disease Amylases Molecular Medicine Acute pancreatitis Cytokines Pituitary Adenylate Cyclase-Activating Polypeptide Tumor necrosis factor alpha medicine.symptom Pancreas business hormones hormone substitutes and hormone antagonists Ceruletide |
| Zdroj: | Journal of Pharmacological Sciences, Vol 110, Iss 4, Pp 451-458 (2009) |
| ISSN: | 1347-8613 |
| Popis: | Development of human chronic pancreatitis is associated with intrapancreatic accumulation of pituitary adenylate cyclase–activating polypeptide (PACAP) accompanied with an altered inflammatory response (Michalski et al., Am J Physiol Gastrointest Liver Physiol. 2008;294:G50–G57). To investigate the role of pancreatic PACAP in the development of acute pancreatitis, we employed transgenic mice over-expressing PACAP in pancreatic β-cells (PACAP-Tg). In comparison to wild-type mice, PACAP-Tg mice exhibited more severe pathophysiological signs of the cerulein-induced pancreatitis at 12 h, as evidenced by higher serum amylase and lipase levels accompanied by the exacerbation of pancreatic edema, necrosis, and inflammation. Cerulein treatment increased mRNA expression of several proinflammatory cytokines (TNFα, IL-1β, and IL-6) at 12 h with similar magnitude both in wild-type and PACAP-Tg mice. In addition, the mRNA and protein levels of regenerating gene III β (RegIIIβ), a key factor in the pancreatic response to acute pancreatitis, were up-regulated at 24 h in wild-type mice upon cerulein administration, whereas they were attenuated in PACAP-Tg mice. These data indicate that over-expressed PACAP in pancreas enhances the cerulein-induced inflammatory response of both acinar cells, leading to aggravated acute pancreatitis, which was accompanied by a down-regulation of RegIIIβ, an anti-inflammatory factor. Keywords:: pituitary adenylate cyclase–activating polypeptide (PACAP), cerulein, acute pancreatitis, regenerating gene III β (RegIIIβ) |
| Databáze: | OpenAIRE |
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