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Pyrrolidine Dithiocarbamate Inhibits Nuclear Factor kappaB and Toll-Like Receptor 4 Expression in Rats with Acute Necrotizing Pancreatitis
Gut and Liver ; : 411-416, 2015.
Article in English | WPRIM | ID: wpr-142460
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.
Subject(s)

Full text: Available Index: WPRIM (Western Pacific) Main subject: Pancreas / Pyrrolidines / Thiocarbamates / RNA, Messenger / Random Allocation / NF-kappa B / Interleukin-6 / Tumor Necrosis Factor-alpha / Rats, Sprague-Dawley / Pancreatitis, Acute Necrotizing Limits: Animals Language: English Journal: Gut and Liver Year: 2015 Type: Article

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Full text: Available Index: WPRIM (Western Pacific) Main subject: Pancreas / Pyrrolidines / Thiocarbamates / RNA, Messenger / Random Allocation / NF-kappa B / Interleukin-6 / Tumor Necrosis Factor-alpha / Rats, Sprague-Dawley / Pancreatitis, Acute Necrotizing Limits: Animals Language: English Journal: Gut and Liver Year: 2015 Type: Article