Attenuated cerulein-induced pancreatitis in nuclear factor-kappaB-deficient mice.
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.
Altavilla
Domenica
D
Department of Clinical and Experimental Medicine and Pharmacology, University of Messina, Italy.
Famulari
Ciro
C
Passaniti
Maria
M
Galeano
Mariarosaria
M
Macrì
Antonio
A
Seminara
Paolo
P
Minutoli
Letteria
L
Marini
Herbert
H
Calò
Margherita
M
Venuti
Francesco S
FS
Esposito
Maria
M
Squadrito
Francesco
F
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
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