title: Attenuated cerulein-induced pancreatitis in nuclear factor-kappaB-deficient mice.
abstract: Nuclear factor (NF)-kappaB plays a central role in acute pancreatitis. We studied cerulein (CER)-induced pancreatitis in NF-kappaB knockout (KO) mice. NF-kappaB KO mice and normal control littermate wild-type (WT) mice were given four hyperstimulating doses of cerulein every hour to elicit secreatagogue-induced pancreatitis. Malonildialdehyde activity, glutathione levels, myeloperoxidase activity, TNF-alpha, and NF-kappaB binding activity and its inhibitory protein IkappaBalpha were studied in the pancreas. Furthermore, we measured plasma lipase and amylase and the histological damage. KO mice had reduced malonildialdehyde levels (WT + CER = 4.083 +/- 0.95 micromol/g; KO + CER = 1.513 +/- 0.63 microol/g), decreased myeloperoxidase activity (WT + CER = 19.3 +/- 2.39 mU/g; KO + CER = 10.21 +/- 2.05 mU/g), increased glutathione levels (WT + CER 6.22 +/- 2.46 micromol/g; KO + CER = 15. 516 +/- 2.92 micromol/g), and reduced serum levels of amylase (WT + CER = 2519 +/- 656.9 U/L; KO + CER = 916 +/- 280.4 U/L) and lipase (WT + CER = 1420 +/- 170 U/L; KO + CER = 861 +/- 172. 3 U/L). KO mice showed reduced pancreatic NF-kappaB activation, decreased TNF-alpha tissue content, and reduced histologic alterations. Our data suggest that KO mice have an attenuated cerulein-induced pancreatitis and help to define the possible interaction between NF-kappaB activation and oxidative stress in this deleterious event.
authors.affiliation: Department of Clinical and Experimental Medicine and Pharmacology, University of Messina, Italy.
authors.forename: Domenica
authors.initials: D
authors.lastname: Altavilla
authors.forename: Ciro
authors.initials: C
authors.lastname: Famulari
authors.forename: Maria
authors.initials: M
authors.lastname: Passaniti
authors.forename: Mariarosaria
authors.initials: M
authors.lastname: Galeano
authors.forename: Antonio
authors.initials: A
authors.lastname: Macrì
authors.forename: Paolo
authors.initials: P
authors.lastname: Seminara
authors.forename: Letteria
authors.initials: L
authors.lastname: Minutoli
authors.forename: Herbert
authors.initials: H
authors.lastname: Marini
authors.forename: Margherita
authors.initials: M
authors.lastname: Calò
authors.forename: Francesco S
authors.initials: FS
authors.lastname: Venuti
authors.forename: Maria
authors.initials: M
authors.lastname: Esposito
authors.forename: Francesco
authors.initials: F
authors.lastname: Squadrito
mesh_terms: D000208:Acute Disease; D000681:Amylases / Q000097:blood; D000818:Animals; D002108:Ceruletide / Q000494:pharmacology*; D004195:Disease Models, Animal; D005978:Glutathione / Q000378:metabolism; D008049:Lipase / Q000097:blood; D008233:Lymphotoxin-alpha / Q000378:metabolism; D008315:Malondialdehyde / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D016328:NF-kappa B / Q000172:deficiency / Q000378:metabolism*; D010179:Pancreas / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D010195:Pancreatitis / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D009195:Peroxidase / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D008233:Lymphotoxin-alpha; D016328:NF-kappa B; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D008315:Malondialdehyde; D002108:Ceruletide; D009195:Peroxidase; D008049:Lipase; D000681:Amylases; D005978:Glutathione