title: Pyrrolidine Dithiocarbamate Inhibits Nuclear Factor κB and Toll-Like Receptor 4 Expression in Rats with Acute Necrotizing Pancreatitis.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Gastroenterology, Shanghai First People's Hospital, Shanghai JiaoTong University, Shanghai, China.
authors.forename: Min
authors.initials: M
authors.lastname: Xu
authors.affiliation: Department of Gastroenterology, Shanghai First People's Hospital, Shanghai JiaoTong University, Shanghai, China.
authors.forename: Kun-Ning
authors.initials: KN
authors.lastname: Wang
authors.affiliation: Department of Gastroenterology, Shanghai First People's Hospital, Shanghai JiaoTong University, Shanghai, China.
authors.forename: Kai
authors.initials: K
authors.lastname: Wu
authors.affiliation: Department of Gastroenterology, Shanghai First People's Hospital, Shanghai JiaoTong University, Shanghai, China.
authors.forename: Xing-Peng
authors.initials: XP
authors.lastname: Wang
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D053583:Interleukin-1beta / Q000235:genetics / Q000378:metabolism; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D008297:Male; D016328:NF-kappa B / Q000187:drug effects* / Q000378:metabolism; D010179:Pancreas / Q000378:metabolism / Q000473:pathology; D019283:Pancreatitis, Acute Necrotizing / Q000139:chemically induced / Q000188:drug therapy*; D011759:Pyrrolidines / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D013859:Thiocarbamates / Q000494:pharmacology*; D051197:Toll-Like Receptor 4 / Q000187:drug effects* / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
chemical_list: D000975:Antioxidants; C000594089:IL1B protein, rat; D053583:Interleukin-1beta; D015850:Interleukin-6; D016328:NF-kappa B; D011759:Pyrrolidines; D012333:RNA, Messenger; D013859:Thiocarbamates; C495347:Tlr4 protein, rat; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha; C020972:pyrrolidine dithiocarbamic acid
keywords: Acute necrotizing pancreatitis; NF-kappa B; Toll-like receptor 4