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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

Nuclear factor κB expression in the pancreas. (A) Acute necrotizing pancreatitis (ANP) group, (B) ANP with pyrrolidine dithiocarbamate pretreatment group, and (C) sham-operation control group (A, B, and C, H&E stain, ×200).
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f2-gnl-09-411: Nuclear factor κB expression in the pancreas. (A) Acute necrotizing pancreatitis (ANP) group, (B) ANP with pyrrolidine dithiocarbamate pretreatment group, and (C) sham-operation control group (A, B, and C, H&E stain, ×200).

Mentions: The immunobiochemistry results indicated that TLR4 expression in rat pancreas was mainly from vascular system, while there was no TLR4 expression in acinar cells. TLR4 positive rate was significantly higher in ANP than in ANP with PDTC treatment and sham-operation group (Table 3, Fig. 1). In sham-operation controls, NF-κB expression was almost depleted from acinar cell nucleus and only seen in a few acinar cell cytosol. But in ANP group, strong NF-κB expression were detected in both acinar cell nucleus and cytosol, while in PDTC pretreated ANP group, NF-κB positive rate is much lower than that in ANP group (Table 4, Fig. 2).


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)

Nuclear factor κB expression in the pancreas. (A) Acute necrotizing pancreatitis (ANP) group, (B) ANP with pyrrolidine dithiocarbamate pretreatment group, and (C) sham-operation control group (A, B, and C, H&E stain, ×200).
© Copyright Policy
Related In: Results  -  Collection

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

f2-gnl-09-411: Nuclear factor κB expression in the pancreas. (A) Acute necrotizing pancreatitis (ANP) group, (B) ANP with pyrrolidine dithiocarbamate pretreatment group, and (C) sham-operation control group (A, B, and C, H&E stain, ×200).
Mentions: The immunobiochemistry results indicated that TLR4 expression in rat pancreas was mainly from vascular system, while there was no TLR4 expression in acinar cells. TLR4 positive rate was significantly higher in ANP than in ANP with PDTC treatment and sham-operation group (Table 3, Fig. 1). In sham-operation controls, NF-κB expression was almost depleted from acinar cell nucleus and only seen in a few acinar cell cytosol. But in ANP group, strong NF-κB expression were detected in both acinar cell nucleus and cytosol, while in PDTC pretreated ANP group, NF-κB positive rate is much lower than that in ANP group (Table 4, Fig. 2).

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