[Effect of MG-132 upon the expression of intercellular adhesion molecule-1 in cerulein-induced acute pancreatitis in mice].
OBJECTIVE
To investigate the effects of the proteasome inhibitor MG-132 upnon NF-kappaB and the expression of intercellular adhesion molecule-1 (ICAM-1) in cerulein-induced acute pancreatitis (AP) in mice.


METHODS
Forty-five BalB/c mice were randomly allocated into nine groups: control 3, 6, 12 h group (n = 5); AP 3, 6, 12 h group (n = 5) and MG-132 3, 6, 12 h group (n = 5). AP group was induced by an ip injection of 100 microg/kg cerulein six times with a 1 h interval. Control group received physiological saline likewise. MG-132 group was injected ip with 10 mg/kg MG-132 at 30 min before induction of AP. The levels of serum amylase and soluble ICAM-1 (sICAM-1) were tested. The pathological changes of pancreas were observed. The expression of NF-kappaB proteins was examined by immunohistochemistry and the expression of ICAM-1 mRNA analyzed by reverse transcription-polymerase chain reaction (RT-PCR).


RESULTS
In MG-132 group, the levels of serum amylase (U/L) and sICAM-1 (pg/ml) markedly decreased in comparison with AP group (1629 +/- 59, 1794 +/- 123, 2910 +/- 152 vs 1282 +/- 61, 1525 +/- 103, 1809 +/- 117, 133 +/- 10, 157 +/- 10, 217 +/- 43 vs 106 +/- 6, 135 +/- 4, 163 +/- 19, P < 0.05 or P < 0.01); the scores of pathological changes decreased in pancreas (5.7 +/- 1.0, 7.1 +/- 1.2, 9.6 +/- 2.1 vs 3.2 +/- 1.0, 5.3 +/- 1.0, 6.9 +/- 0.8, P < 0.05 or P < 0.01);the expression of NF-kappaB protein (3.8 +/- 1.1, 4.6 +/- 1.2, 6.7 +/- 0.4 vs 1.9 +/- 0.6, 3.1 +/- 1.0, 4.7 +/- 1.0, P < 0.05 or P < 0.01) were significantly lowered than those in AP group. ICAM-1 mRNA also decreased more than those in AP group (0.3 +/- 0.1, 1.0 +/- 0.2, 1.2 +/- 1.0 vs 0.3 +/- 0.2, 1.8 +/- 0.2, 2.1 +/- 0.2, P < 0.05 or P < 0.01).


CONCLUSIONS
The proteasome inhibitor MG-132 can obviously improve the outcome of acute pancreatitis. And the mechanism may be related to the down-regulated expression of cytokines, including adhesion molecules, through the suppression of NF-kappaB activation.
Xu
Chun-fang
CF
Department of Gastroenterology, First Affiliated Hospital of Soochow University, Suzhou 215006, China. xcf601@163.com
Xia
Shu-jing
SJ
D000818:Animals; D002108:Ceruletide / Q000009:adverse effects; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism*; D007976:Leupeptins / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D016328:NF-kappa B / Q000378:metabolism; D019283:Pancreatitis, Acute Necrotizing / Q000139:chemically induced / Q000378:metabolism*
C090509:Icam1 protein, mouse; D007976:Leupeptins; D016328:NF-kappa B; D018799:Intercellular Adhesion Molecule-1; D002108:Ceruletide; C072553:benzyloxycarbonylleucyl-leucyl-leucine aldehyde