title: Activation of interleukin-6/STAT3 in rat cholangiocyte proliferation induced by lipopolysaccharide.
abstract: BACKGROUND
  Cholangiocytes are exposed to endotoxins (lipopolysaccharide, LPS) in a variety of biliary inflammations. It is known that LPS enhances the release of interleukin (IL)-6, a potent cholangiocyte mitogen. However, the role of LPS in cholangiocyte proliferation in vivo is unknown. Aims To investigate whether LPS stimulates cholangiocyte proliferation in vivo via the IL-6/STAT3 pathway.
  
  
  METHODS
  Rats were randomized into four groups: the LPS group (injected intravenously with LPS 2.5 mg/kg), anti-IL-6 group (injected intravenously with anti-IL-6 0.5 mg/kg 1 h after LPS injection), RPM group (treated with RPM 0.4 mg/kg intraperitoneally 30 min before LPS injection), and control group. At 6, 12, 24, 48, and 72 h after LPS injection, LPS in plasma was detected by kinetic turbidimetric limulus test. IL-6 concentrations in liver homogenate and cholangiocyte proliferation were determined by ELISA or immunohistochemistry, respectively. Expression of IL-6 mRNA and phosphorylated-STAT3 (P-STAT3) protein in cholangiocytes was analyzed by real-time RT-PCR and western blotting.
  
  
  RESULTS
  Cholangiocytes responded to LPS by a marked increase in cell proliferation, IL-6 secretion, and P-STAT3 expression. Anti-IL-6 neutralizing antibody inhibited LPS-induced proliferation of cholangiocytes and decreased levels of IL-6 and STAT3. Furthermore, after being treated with RPM, STAT3 activation was also depressed, which resulted a decreased proliferation of cholangiocytes.
  
  
  CONCLUSIONS
  LPS promotes cholangiocyte proliferation through the IL-6/STAT3 pathway, while RPM shows a depressive effect in this pathway.
authors.affiliation: Organ Transplantation Center, Second Hospital Affiliated to General Hospital of PLA, Beijing, 100091, China.
authors.forename: Li-Ping
authors.initials: LP
authors.lastname: Chen
authors.forename: Ming
authors.initials: M
authors.lastname: Cai
authors.forename: Qi-Hao
authors.initials: QH
authors.lastname: Zhang
authors.forename: Zhou-Li
authors.initials: ZL
authors.lastname: Li
authors.forename: Ye-Yong
authors.initials: YY
authors.lastname: Qian
authors.forename: Hong-Wei
authors.initials: HW
authors.lastname: Bai
authors.forename: Xing
authors.initials: X
authors.lastname: Wei
authors.forename: Bing-Yi
authors.initials: BY
authors.lastname: Shi
authors.forename: Jia-Hong
authors.initials: JH
authors.lastname: Dong
mesh_terms: D000818:Animals; D001653:Bile Ducts, Intrahepatic / Q000166:cytology*; D049109:Cell Proliferation; D004847:Epithelial Cells / Q000502:physiology*; D007166:Immunosuppressive Agents / Q000494:pharmacology; D015850:Interleukin-6 / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000097:blood / Q000494:pharmacology; D008099:Liver / Q000378:metabolism; D008297:Male; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D050796:STAT3 Transcription Factor / Q000037:antagonists & inhibitors / Q000378:metabolism*; D020123:Sirolimus / Q000494:pharmacology
chemical_list: D007166:Immunosuppressive Agents; D015850:Interleukin-6; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D050796:STAT3 Transcription Factor; C494088:Stat3 protein, rat; D020123:Sirolimus