title: Hepatitis B virus particles preferably induce Kupffer cells to produce TGF-β1 over pro-inflammatory cytokines.
abstract: BACKGROUND
  Kupffer cells and related cytokines are thought to play a critical role in liver fibrosis; however, the role played by Kupffer cells in hepatitis B virus-related fibrogenesis is unknown.
  
  
  METHODS
  Primary rat Kupffer cells were cultured with different titres of hepatitis B virus particles and the concentrations of transforming growth factor (TGF)-β1, interleukin (IL)-1, IL-6 and tumour necrosis factor (TNF)-α in the culture supernatant were measured every 24h for 7 days. The mRNA and protein levels of these cytokines in Kupffer cells were also analysed using quantitative real-time polymerase chain reaction and western blotting, respectively.
  
  
  RESULTS
  Kupffer cells maintained normal morphology and function throughout the 7-day exposure to hepatitis B virus. The concentration of TGF-β1 secreted by hepatitis B virus-stimulated Kupffer cells (6 log IU/ml hepatitis B virus) increased 5.38- and 7.75-fold by Days 3 and 7, respectively (p<0.01). Western blotting showed that TGF-β1 expression in Kupffer cells exposed to high titres of hepatitis B virus increased 1.80- and 2.42-fold by Days 3 and 7, respectively (p<0.01). In contrast, Kupffer cell expression and secretion of pro-inflammatory cytokines (IL-6, IL-1 and TNF-α) was unchanged throughout the experiment.
  
  
  CONCLUSIONS
  Hepatitis B virus preferentially stimulates Kupffer cells to produce the pro-fibrogenic/anti-inflammatory cytokine TGF-β1 rather than the pro-inflammatory cytokines IL-6, IL-1 and TNF-α. This may partly explain why overt liver fibrosis still presents in cases of chronic hepatitis B virus infection with minimal (or no) necro-inflammation.
authors.affiliation: Liver Research Center, Beijing Friendship Hospital, Capital Medical University, Beijing, PR China.
authors.forename: Hai
authors.initials: H
authors.lastname: Li
authors.forename: Huan-Wei
authors.initials: HW
authors.lastname: Zheng
authors.forename: Hui
authors.initials: H
authors.lastname: Chen
authors.forename: Zhi-Zhi
authors.initials: ZZ
authors.lastname: Xing
authors.forename: Hong
authors.initials: H
authors.lastname: You
authors.forename: Min
authors.initials: M
authors.lastname: Cong
authors.forename: Ji-Dong
authors.initials: JD
authors.lastname: Jia
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D049109:Cell Proliferation; D002478:Cells, Cultured; D005355:Fibrosis / Q000378:metabolism; D006515:Hepatitis B virus; D007375:Interleukin-1 / Q000096:biosynthesis; D015850:Interleukin-6 / Q000096:biosynthesis; D007728:Kupffer Cells / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D008297:Male; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017208:Rats, Wistar; D053773:Transforming Growth Factor beta1 / Q000096:biosynthesis*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
chemical_list: D007375:Interleukin-1; D015850:Interleukin-6; D012333:RNA, Messenger; D053773:Transforming Growth Factor beta1; D014409:Tumor Necrosis Factor-alpha