Pyrrolidine Dithiocarbamate Inhibits Nuclear Factor kappaB and Toll-Like Receptor 4 Expression in Rats with Acute Necrotizing Pancreatitis.
- Author:
Min XU
1
,
2
;
Kun Ning WANG
;
Kai WU
;
Xing Peng WANG
Author Information
- Publication Type:Original Article
- Keywords: Acute necrotizing pancreatitis; NF-kappa B; Toll-like receptor 4
- MeSH: Animals; Antioxidants/*pharmacology; Interleukin-1beta/genetics/metabolism; Interleukin-6/genetics/metabolism; Male; NF-kappa B/*drug effects/metabolism; Pancreas/metabolism/pathology; Pancreatitis, Acute Necrotizing/chemically induced/*drug therapy; Pyrrolidines/*pharmacology; RNA, Messenger/metabolism; Random Allocation; Rats; Rats, Sprague-Dawley; Thiocarbamates/*pharmacology; Toll-Like Receptor 4/*drug effects/metabolism; Tumor Necrosis Factor-alpha/genetics/metabolism
- From:Gut and Liver 2015;9(3):411-416
- CountryRepublic of Korea
- Language:English
- Abstract: BACKGROUND/AIMS: To investigate the expression of Toll-like receptor 4 (TLR4) in the pancreases of rats with acute necrotizing pancreatitis (ANP) and any changes upon treatment with pyrrolidine dithiocarbamate (PDTC), an inhibitor of nuclear factor kappaB (NF-kappaB), as well as to determine the relationship between TLR4 and NF-kappaB in ANP pathogenesis. METHODS: A total of 72 SD rats were randomly divided into three groups, namely, the control (sham-operation), ANP, and ANP with PDTC pretreatment groups. The PDTC-pretreated group was intraperitoneally injected with PDTC at a dose of 100 mg/kg 1 hour before the induction of ANP. The expressions of TLR4 and NF-kappaB in pancreatic tissue were evaluated by immunohistochemistry and Western blot analysis. The mRNA levels of cytokines tumor necrosis factor alpha, interleukin (IL)-1beta, and IL-6 were measured by reverse transcription polymerase chain reaction. RESULTS: The expressions of TLR4, NF-kappaB, and cytokine (NF-kappaB target) genes in the pancreatic tissue increased more significantly in the ANP groups than in the sham-operation group at 3, 6, and 12 hours. Pretreatment with PDTC alleviated the inflammatory activation in the pancreas with ANP, causing a significant decrease in the expressions of TLR4, NF-kappaB, and cytokine genes in the pancreatic tissue. CONCLUSIONS: The expressions of TLR4 and NF-kappaB were increased in the pancreases of rats with ANP. PDTC not only inhibits NF-kappaB but also suppresses the expression of TLR4 and downregulates the expression of the related cytokine genes.
