title: L-cysteine administration attenuates pancreatic fibrosis induced by TNBS in rats by inhibiting the activation of pancreatic stellate cell.
abstract: OBJECTIVE
  Recent studies have shown that activated pancreatic stellate cells (PSCs) play a major role in pancreatic fibrogenesis. We aimed to study the effect of L-cysteine administration on fibrosis in chronic pancreatitis (CP) induced by trinitrobenzene sulfonic acid (TNBS) in rats and on the function of cultured PSCs.
  
  
  METHODS
  CP was induced by TNBS infusion into rat pancreatic ducts. L-cysteine was administrated for the duration of the experiment. Histological analysis and the contents of hydroxyproline were used to evaluate pancreatic damage and fibrosis. Immunohistochemical analysis of α-SMA in the pancreas was performed to detect the activation of PSCs in vivo. The collagen deposition related proteins and cytokines were determined by western blot analysis. DNA synthesis of cultured PSCs was evaluated by BrdU incorporation. We also evaluated the effect of L-cysteine on the cell cycle and cell activation by flow cytometry and immunocytochemistry. The expression of PDGFRβ, TGFβRII, collagen 1α1 and α-SMA of PSCs treated with different concentrations of L-cysteine was determined by western blot. Parameters of oxidant stress were evaluated in vitro and in vivo. Nrf2, NQO1, HO-1, IL-1β expression were evaluated in pancreas tissues by qRT-PCR.
  
  
  RESULTS
  The inhibition of pancreatic fibrosis by L-cysteine was confirmed by histological observation and hydroxyproline assay. α-SMA, TIMP1, IL-1β and TGF-β1 production decreased compared with the untreated group along with an increase in MMP2 production. L-cysteine suppressed the proliferation and extracellular matrix production of PSCs through down-regulating of PDGFRβ and TGFβRII. Concentrations of MDA+4-HNE were decreased by L-cysteine administration along with an increase in GSH levels both in tissues and cells. In addition, L-cysteine increased the mRNA expression of Nrf2, NQO1 and HO-1 and reduced the expression of IL-1β in L-cysteine treated group when compared with control group.
  
  
  CONCLUSIONS
  L-cysteine treatment attenuated pancreatic fibrosis in chronic pancreatitis in rats.
authors.affiliation: Department of Gastroenterology, The First People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China.
authors.forename: LiJuan
authors.initials: L
authors.lastname: Yang
authors.forename: JiaQing
authors.initials: J
authors.lastname: Shen
authors.forename: ShanShan
authors.initials: S
authors.lastname: He
authors.forename: GuoYong
authors.initials: G
authors.lastname: Hu
authors.forename: Jie
authors.initials: J
authors.lastname: Shen
authors.forename: Feng
authors.initials: F
authors.lastname: Wang
authors.forename: Ling
authors.initials: L
authors.lastname: Xu
authors.forename: WeiQi
authors.initials: W
authors.lastname: Dai
authors.forename: Jie
authors.initials: J
authors.lastname: Xiong
authors.forename: JianBo
authors.initials: J
authors.lastname: Ni
authors.forename: ChuanYong
authors.initials: C
authors.lastname: Guo
authors.forename: Rong
authors.initials: R
authors.lastname: Wan
authors.forename: XingPeng
authors.initials: X
authors.lastname: Wang
mesh_terms: D000818:Animals; D003545:Cysteine / Q000627:therapeutic use*; D005355:Fibrosis / Q000139:chemically induced / Q000188:drug therapy*; D010182:Pancreatic Diseases / Q000188:drug therapy*; D058954:Pancreatic Stellate Cells / Q000187:drug effects*; D050500:Pancreatitis, Chronic / Q000188:drug therapy / Q000473:pathology; D051381:Rats; D016896:Treatment Outcome; D014302:Trinitrobenzenesulfonic Acid
chemical_list: D014302:Trinitrobenzenesulfonic Acid; D003545:Cysteine