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Pyrrolidine Dithiocarbamate Inhibits Nuclear Factor κB and Toll-Like Receptor 4 Expression in Rats with Acute Necrotizing Pancreatitis.

Xu M, Wang KN, Wu K, Wang XP - Gut Liver (2015)

Bottom Line: The expressions of TLR4, NF-κB, and cytokine (NF-κB 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-κB, and cytokine genes in the pancreatic tissue.PDTC not only inhibits NF-κB but also suppresses the expression of TLR4 and downregulates the expression of the related cytokine genes.

View Article: PubMed Central - PubMed

Affiliation: Department of Gastroenterology, Shanghai First People's Hospital, Shanghai JiaoTong University, Shanghai, China.

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 κB (NF-κB), as well as to determine the relationship between TLR4 and NF-κB 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-κB in pancreatic tissue were evaluated by immunohistochemistry and Western blot analysis. The mRNA levels of cytokines tumor necrosis factor α, interleukin (IL)-β, and IL-6 were measured by reverse transcription polymerase chain reaction.

Results: The expressions of TLR4, NF-κB, and cytokine (NF-κB 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-κB, and cytokine genes in the pancreatic tissue.

Conclusions: The expressions of TLR4 and NF-κB were increased in the pancreases of rats with ANP. PDTC not only inhibits NF-κB but also suppresses the expression of TLR4 and downregulates the expression of the related cytokine genes.

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Related in: MedlinePlus

Electrophoresis of reverse transcription polymerase chain reaction results of the tumor necrosis factor α (TNF-α), interleukin (IL)-1β, and IL-6 mRNA in the rat pancreas. ANP, acute necrotizing pancreatitis; PDTC, pyrrolidine dithiocarbamate.
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f4-gnl-09-411: Electrophoresis of reverse transcription polymerase chain reaction results of the tumor necrosis factor α (TNF-α), interleukin (IL)-1β, and IL-6 mRNA in the rat pancreas. ANP, acute necrotizing pancreatitis; PDTC, pyrrolidine dithiocarbamate.

Mentions: Electrophoresis of semi-quantitative RT-PCR result was shown in Fig. 4. In ANP rat group, TNF-α and IL-6 were higher at 3 hours than at 6 hours or 12 hours at mRNA level (p<0.05), while mRNA expression level of IL-1β was much higher at 12 hours than at 3 hours or 6 hours (p<0.05). In PDTC pretreated ANP group, mRNA of TNF-α, IL-1β, and IL-6 were all expressed at a decreased level compared with that in ANP group. A closer examination revealed that in comparison with ANP group, TNF-α mRNA level was significantly lower in PDTC pretreated group at 6 hours time point (p<0.05), IL-1β mRNA expression was obviously lower at 6 hours and 12 hours time points (p<0.05), and IL-6 mRNA expression was lower at 3 hours time point (p<0.05).


Pyrrolidine Dithiocarbamate Inhibits Nuclear Factor κB and Toll-Like Receptor 4 Expression in Rats with Acute Necrotizing Pancreatitis.

Xu M, Wang KN, Wu K, Wang XP - Gut Liver (2015)

Electrophoresis of reverse transcription polymerase chain reaction results of the tumor necrosis factor α (TNF-α), interleukin (IL)-1β, and IL-6 mRNA in the rat pancreas. ANP, acute necrotizing pancreatitis; PDTC, pyrrolidine dithiocarbamate.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4413976&req=5

f4-gnl-09-411: Electrophoresis of reverse transcription polymerase chain reaction results of the tumor necrosis factor α (TNF-α), interleukin (IL)-1β, and IL-6 mRNA in the rat pancreas. ANP, acute necrotizing pancreatitis; PDTC, pyrrolidine dithiocarbamate.
Mentions: Electrophoresis of semi-quantitative RT-PCR result was shown in Fig. 4. In ANP rat group, TNF-α and IL-6 were higher at 3 hours than at 6 hours or 12 hours at mRNA level (p<0.05), while mRNA expression level of IL-1β was much higher at 12 hours than at 3 hours or 6 hours (p<0.05). In PDTC pretreated ANP group, mRNA of TNF-α, IL-1β, and IL-6 were all expressed at a decreased level compared with that in ANP group. A closer examination revealed that in comparison with ANP group, TNF-α mRNA level was significantly lower in PDTC pretreated group at 6 hours time point (p<0.05), IL-1β mRNA expression was obviously lower at 6 hours and 12 hours time points (p<0.05), and IL-6 mRNA expression was lower at 3 hours time point (p<0.05).

Bottom Line: The expressions of TLR4, NF-κB, and cytokine (NF-κB 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-κB, and cytokine genes in the pancreatic tissue.PDTC not only inhibits NF-κB but also suppresses the expression of TLR4 and downregulates the expression of the related cytokine genes.

View Article: PubMed Central - PubMed

Affiliation: Department of Gastroenterology, Shanghai First People's Hospital, Shanghai JiaoTong University, Shanghai, China.

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 κB (NF-κB), as well as to determine the relationship between TLR4 and NF-κB 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-κB in pancreatic tissue were evaluated by immunohistochemistry and Western blot analysis. The mRNA levels of cytokines tumor necrosis factor α, interleukin (IL)-β, and IL-6 were measured by reverse transcription polymerase chain reaction.

Results: The expressions of TLR4, NF-κB, and cytokine (NF-κB 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-κB, and cytokine genes in the pancreatic tissue.

Conclusions: The expressions of TLR4 and NF-κB were increased in the pancreases of rats with ANP. PDTC not only inhibits NF-κB but also suppresses the expression of TLR4 and downregulates the expression of the related cytokine genes.

Show MeSH
Related in: MedlinePlus