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Journal of Molecular Medicine

, Volume 88, Issue 10, pp 1055–1063 | Cite as

PKC δ mediates pro-inflammatory responses in a mouse model of caerulein-induced acute pancreatitis

  • Raina Devi Ramnath
  • Jia Sun
  • Madhav BhatiaEmail author
Original Article

Abstract

Acute pancreatitis is an inflammatory disorder of the pancreas. Protein kinase C (PKC) δ plays an important role in mediating chemokine production in mouse pancreatic acinar cells. This study aims to investigate the role of PKC δ in the pathogenesis of acute pancreatitis and to explore the mechanisms through which PKC δ mediates pro-inflammatory signaling. Acute pancreatitis was induced in mice by ten hourly intraperitoneal injections of caerulein. PKC δ translocation inhibitor peptide (δV1-1) at a dose of 1.0 mg/kg or Tat (carrier peptide) at a dose of 1.0 mg/kg was administered to mice either 1 h before or 1 h after the first caerulein injection. One hour after the last caerulein injection, the mice were killed and pancreas, lungs, and blood were collected. Prophylactic and therapeutic treatment with δV1-1 attenuated caerulein-induced plasma amylase levels and pancreatic edema. Treatment with δV1-1 decreased myeloperoxidase activity and monocyte chemotactic protein-1 levels in both pancreas and plasma. PKC δ mediated acute pancreatitis by activating pancreatic nuclear factor κB, activator protein-1, and mitogen-activated protein kinases. Moreover, blockade of PKC δ attenuated lung myeloperoxidase activity and edema. Histological examination of pancreatic and lung sections confirmed protection against acute pancreatitis. Treatment with Tat had no protective effect on acute pancreatitis. Blockade of PKC δ represents a promising prophylactic and/or therapeutic tool for the treatment of acute pancreatitis.

Keywords

Acute pancreatitis PKC δ Pancreatic acinar cells Chemokine Pancreas Pathology Inflammation 

Notes

Acknowledgements

We would like to give our thanks to Mei Leng Shoon for technical assistance. This work was supported by the National Medical Research Council grant no. R-184-000-156-213.

Disclosure

The authors have nothing to disclose and have no conflict of interest.

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Copyright information

© Springer-Verlag 2010

Authors and Affiliations

  1. 1.Department of PharmacologyNational University of SingaporeSingaporeSingapore
  2. 2.Department of PathologyUniversity of Otago, ChristchurchChristchurchNew Zealand

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