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World J Gastroenterol. Nov 28, 2014; 20(44): 16535-16543
Published online Nov 28, 2014. doi: 10.3748/wjg.v20.i44.16535
Evidence for a role of mitogen-activated protein kinases in the treatment of experimental acute pancreatitis
Natasha Irrera, Alessandra Bitto, Monica Interdonato, Francesco Squadrito, Domenica Altavilla
Natasha Irrera, Alessandra Bitto, Monica Interdonato, Francesco Squadrito, Department of Clinical and Experimental Medicine, University of Messina, 98125 Messina, Italy
Domenica Altavilla, Department of Paediatric, Gynaecological, Microbiological and Biomedical Sciences, University of Messina, 98125 Messina, Italy
Author contributions: Irrera N and Squadrito F contributed to conception and design; Bitto A, Interdonato M and Altavilla D analysed the data; Irrera N and Bitto A contributed to writing of the paper; Squadrito F, Interdonato M and Altavilla D contributed to revision for intellectual content; Irrera N, Bitto A, Interdonato M, Squadrito F and Altavilla D did the final approval.
Correspondence to: Francesco Squadrito, MD, Professor, Department of Clinical and Experimental Medicine, Section of Pharmacology, University of Messina, Torre Biologica 5th floor, c/o AOU Policlinico G. Martino, Via C. Valeria Gazzi, 98125 Messina, Italy. francesco.squadrito@unime.it
Telephone: +39-90-2213648 Fax: +39-90-2213300
Received: February 28, 2014
Revised: June 23, 2014
Accepted: July 22, 2014
Published online: November 28, 2014
Processing time: 277 Days and 9.4 Hours
Abstract

Acute pancreatitis (AP) is an inflammatory disease characterized by acute inflammation and necrosis of the pancreatic parenchyma. AP is often associated with organ failure, sepsis, and high mortality. The pathogenesis of AP is still not well understood. In recent years several papers have highlighted the cellular and molecular events of acute pancreatitis. Pancreatitis is initiated by activation of digestive enzymes within the acinar cells that are involved in autodigestion of the gland, followed by a massive infiltration of neutrophils and macrophages and release of inflammatory mediators, responsible for the local and systemic inflammatory response. The hallmark of AP is parenchymal cell necrosis that represents the cause of the high morbidity and mortality, so that new potential therapeutic approaches are indispensable for the treatment of patients at high risk of complications. However, not all factors that determine the onset and course of the disease have been explained. Aim of this article is to review the role of mitogen-activated protein kinases in pathogenesis of acute pancreatitis.

Keywords: Experimental acute pancreatitis; Mitogen-activated protein kinases; Mitogen-activated protein kinases inhibitors; Cytokines; Cholecystokinin; Cerulein

Core tip: The review focuses on the role of mitogen-activated protein kinases (MAPKs) in the treatment of acute pancreatitis. In fact, acute pancreatitis is a disease characterized by a marked inflammatory reaction and it is usually associated with severe upper abdominal pain, organ failure and also mortality. The activation of MAPKs is an early event in AP and exerts a central role in the onset and development of acute pancreatitis. Thanks to the pivotal function played by MAPKs in acute pancreatitis, the use of specific inhibitors may represent a potential therapeutic target for the treatment of this inflammatory disease.