PMID- 15586409
OWN - NLM
STAT- MEDLINE
DCOM- 20051115
LR  - 20211203
IS  - 1008-9292 (Print)
IS  - 1008-9292 (Linking)
VI  - 33
IP  - 6
DP  - 2004 Nov
TI  - [The active metabolite of leflunomide A771726 inhibits proliferation and collagen 
      synthesis of hepatic stellate cell].
PG  - 515-8, 528
AB  - OBJECTIVE: To investigate the effect of the metabolite of leflunomide, A771726,on 
      proliferation and collagen synthesis of hepatic stellate cell (HSC). METHODS: HSC 
      and Kupffer cells were isolated from the rat liver by collagenase IV and pronase 
      perfusion, and purified by density gradient separation. The effects of A771726 on 
      cell proliferation and collagen synthesis were examined by 3H-thymidine and 
      3H-proline incorporation assays, respectively. The TGF-beta, TNF-alpha and IL-1 
      levels in Kupffer cell conditioned medium (KCCM) were determined by enzyme-linked 
      immunosorbent assay (ELISA). RESULTS: HSC and Kupffer cells in rat liver were 
      well separated. The KCCM of CCl4-injured rats had significant stimulation effect 
      on proliferation and collagen synthesis of HSC in primary culture. Addition of 
      A771726 (0.001-10 micromol/Lein HSC culture stimulated by KCCM significantly 
      inhibited proliferation and collagen synthesis of HSC. Furthermore, the elevated 
      TGF-beta, TNF-alpha and IL-1 levels in KCCM of CCl4-injured rats were 
      significantly reduced in A771726 treatment groups. CONCLUSION: A771726 has 
      markedly inhibitory effect on proliferation and collagen synthesis of HSC and 
      secretion of TGF-beta,TNF-alpha and IL-1 from Kupffer cells.
FAU - Yao, Hong-wei
AU  - Yao HW
AD  - Zhejiang Respiratory Drugs Research Laboratory of State Food and Drugs 
      Administration of China, College of Medicine, Zhejiang University, Hangzhou 
      310031, China.
FAU - Li, Jun
AU  - Li J
FAU - Chen, Ji-qiang
AU  - Chen JQ
FAU - Xu, Shu-yun
AU  - Xu SY
LA  - chi
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - China
TA  - Zhejiang Da Xue Xue Bao Yi Xue Ban
JT  - Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical 
      sciences
JID - 100927946
RN  - 0 (Aniline Compounds)
RN  - 0 (Collagen Type I)
RN  - 0 (Crotonates)
RN  - 0 (Hydroxybutyrates)
RN  - 0 (Immunosuppressive Agents)
RN  - 0 (Interleukin-1)
RN  - 0 (Isoxazoles)
RN  - 0 (Nitriles)
RN  - 0 (Toluidines)
RN  - 0 (Transforming Growth Factor beta)
RN  - 1C058IKG3B (teriflunomide)
RN  - CL2T97X0V0 (Carbon Tetrachloride)
RN  - G162GK9U4W (Leflunomide)
SB  - IM
MH  - Aniline Compounds/*pharmacology
MH  - Animals
MH  - Carbon Tetrachloride
MH  - Cell Division/drug effects
MH  - Cells, Cultured
MH  - Collagen Type I/*biosynthesis
MH  - Crotonates
MH  - Hepatocytes/*cytology
MH  - Hydroxybutyrates/*pharmacology
MH  - Immunosuppressive Agents/pharmacology
MH  - Interleukin-1/metabolism
MH  - Isoxazoles/metabolism/*pharmacology
MH  - Kupffer Cells/cytology
MH  - Leflunomide
MH  - Male
MH  - Nitriles
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Toluidines
MH  - Transforming Growth Factor beta/metabolism
EDAT- 2004/12/09 09:00
MHDA- 2005/11/16 09:00
CRDT- 2004/12/09 09:00
PHST- 2004/12/09 09:00 [pubmed]
PHST- 2005/11/16 09:00 [medline]
PHST- 2004/12/09 09:00 [entrez]
AID - 10.3785/j.issn.1008-9292.2004.06.010 [doi]
PST - ppublish
SO  - Zhejiang Da Xue Xue Bao Yi Xue Ban. 2004 Nov;33(6):515-8, 528. doi: 
      10.3785/j.issn.1008-9292.2004.06.010.