ABSTRACT
BACKGROUND: Recently, it has been reported that interleukin 4 (IL-4) and 13 (IL-13) directly activate fibroblasts and promote fibrosis. In the process of hepatic fibrosis, the effects of these cytokines on hepatic stellate cells (HSCs) are not well known. METHODS: We evaluated the effects of IL-4 and IL-13 on the collagen production and the proliferation of LI90, a hepatic stellate cell line. We also examined whether interferon (IFN) interferes with the expression of collagen, since IFN has been reported to clinically suppress hepatic fibrosis. RESULTS: The receptor complex for IL-4 and IL-13 was IL-4Ralpha/IL-13Ralpha1 on LI90 cells, and the phosphorylation of Stat6 was induced by IL-4 and IL-13. The treatment of LI90 cells with IL-4 or IL-13 increased the production of collagen I protein levels by nearly three times in comparison with untreated cells. Collagen mRNA levels were increased roughly 10-fold by IL-4 and 100-fold by IL-13. Interestingly, BrdU incorporation in LI90 cells was decreased by IL-4 or IL-13 treatment. Furthermore, induction of collagen I production by these cytokines was blocked by IFNalpha or IFNbeta treatment, although neither treatment alone suppressed collagen production. CONCLUSIONS: Our data suggested that IL-4 and IL-13 directly affected HSCs by increasing collagen production and suppressing cell proliferation. The anti-fibrogenetic effect of IFN may be due in part to the blockade of IL-4 and IL-13 stimulation of HSCs.
Subject(s)
Cell Proliferation/drug effects , Collagen/biosynthesis , Hepatocytes/cytology , Interleukin-13/pharmacology , Interleukin-4/pharmacology , Base Sequence , Blotting, Western , Cells, Cultured , Collagen/drug effects , Enzyme-Linked Immunosorbent Assay , Hepatocytes/drug effects , Humans , Liver Cirrhosis/pathology , Molecular Sequence Data , Probability , RNA, Messenger/analysis , Reference Values , Reverse Transcriptase Polymerase Chain Reaction , Sensitivity and Specificity , Statistics, NonparametricSubject(s)
Antigens, Neoplasm/blood , Bile Duct Neoplasms/blood , Bile Ducts, Intrahepatic , Biomarkers, Tumor/blood , Cholangiocarcinoma/blood , Neoplasm Recurrence, Local/blood , Pancreatic Neoplasms/blood , Aged , Bile Duct Neoplasms/diagnostic imaging , Bile Duct Neoplasms/surgery , Cholangiocarcinoma/diagnostic imaging , Cholangiocarcinoma/surgery , Female , Humans , Middle Aged , Pancreatic Neoplasms/surgery , Predictive Value of Tests , Tomography, X-Ray ComputedABSTRACT
We report a pancreaticojejunostomy with double duct-to-mucosa anastomotic technique after pyloruspreserving pancreaticoduodenectomy for chronic pancreatitis with bifid pancreatic duct. A 49-year-old Japanese man was diagnosed preoperatively as having chronic pancreatitis with common bile duct stricture and pseudocyst of the pancreatic head. In a pancreaticoduodenectomy, the main pancreatic duct (7mm in diameter) and a secondary pancreatic duct (4mm in diameter) were identified intraoperatively at the transected surface. Pancreatography showed the main pancreatic duct as well as thesecondary pancreatic duct that drained the remaining dorsal pancreas, allowing us to diagnose bifid pancreatic duct. The pancreaticojejunostomy was performed in an end-to-side manner to create double duct-to-mucosa anastomoses and to approximate the pancreatic parenchyma and jejunal seromuscular layers. Although bifid pancreatic duct is a rare anatomical anomaly, it behooves every surgeon who performs pancreatic resections to be aware of this entity and the techniques for dealing with it.
