title: 5-lipoxygenase knockout mice exhibit a resistance to acute pancreatitis induced by cerulein.
abstract: Here we compare the degree of pancreatitis caused by cerulein in mice lacking 5-lipoxygenase (5-LO) and in the corresponding wild-type mice. Intraperitoneal injection of cerulein in mice resulted in severe, acute pancreatitis characterized by oedema, neutrophil infiltration and necrosis and elevated serum levels of amylase and lipase. Infiltration of pancreatic and lung tissue with neutrophils (measured as increase in myeloperoxidase activity) was associated with enhanced lipid peroxidation (increased tissue levels of malondialdehyde). Immunohistochemical examination demonstrated a marked increase in immunoreactivity for intracellular adhesion molecule-1 (ICAM-1), P-selectin and E-selectin in the pancreas and lung of cerulein-treated mice. In contrast, the degree of (1) pancreatic inflammation and tissue injury (histological score), (2) up-regulation/expression of P-selectin, E-selectin and ICAM-1, and (3) neutrophil infiltration was markedly reduced in pancreatic and lung tissue obtained from cerulein-treated 5-LO-deficient mice. These findings support the view that 5-LO plays an important, pro-inflammatory role in the acute pancreatitis caused by cerulein in mice.
authors.affiliation: Department of Clinical and Experimental Medicine and Pharmacology, Policlinico Universitario, Messina, Italy. salvator@unime.it
authors.forename: Salvatore
authors.initials: S
authors.lastname: Cuzzocrea
authors.forename: Antonietta
authors.initials: A
authors.lastname: Rossi
authors.forename: Ivana
authors.initials: I
authors.lastname: Serraino
authors.forename: Rosanna
authors.initials: R
authors.lastname: Di Paola
authors.forename: Laura
authors.initials: L
authors.lastname: Dugo
authors.forename: Tiziana
authors.initials: T
authors.lastname: Genovese
authors.forename: Domenico
authors.initials: D
authors.lastname: Britti
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Sciarra
authors.forename: Angelina
authors.initials: A
authors.lastname: De Sarro
authors.forename: Achille P
authors.initials: AP
authors.lastname: Caputi
authors.forename: Lidia
authors.initials: L
authors.lastname: Sautebin
mesh_terms: D000208:Acute Disease; D000818:Animals; D001094:Arachidonate 5-Lipoxygenase / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D002108:Ceruletide; D019040:E-Selectin / Q000378:metabolism; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D015227:Lipid Peroxidation; D008107:Liver Diseases / Q000201:enzymology / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D020556:Neutrophil Infiltration; D019007:P-Selectin / Q000378:metabolism; D010195:Pancreatitis / Q000139:chemically induced / Q000201:enzymology* / Q000473:pathology; D012128:Respiratory Distress Syndrome / Q000201:enzymology / Q000473:pathology
chemical_list: D019040:E-Selectin; D019007:P-Selectin; D018799:Intercellular Adhesion Molecule-1; D002108:Ceruletide; D001094:Arachidonate 5-Lipoxygenase