PMID- 15162534
OWN - NLM
STAT- MEDLINE
DCOM- 20040719
LR  - 20211203
IS  - 1007-9327 (Print)
IS  - 2219-2840 (Electronic)
IS  - 1007-9327 (Linking)
VI  - 10
IP  - 11
DP  - 2004 Jun 1
TI  - Leflunomide attenuates hepatocyte injury by inhibiting Kupffer cells.
PG  - 1608-11
AB  - AIM: To investigate the importance of direct contact between Kupffer cells (KCs) 
      and hepatocytes (HCs) during hepatic inflammatory responses, and the effect of 
      leflunomide's active metabolite, A(771726), on cytokines in KCs, HCs and KC 
      cocultures (DC cocultures). METHODS: KCs and HCs in liver were isolated by 
      digestion with pronase and collagenase. Lipopolysaccharide (LPS)-induced 
      inflammatory response in monocultures of rat HCs and KCs was compared with that 
      in DC cocultures. Tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 
      (IL-1) concentrations in different culture supernatants were measured with ELISA. 
      TNF-alpha mRNA in KCs of inflammatory liver injury was analyzed with reverse 
      transcriptase polymerase chain reaction (RT-PCR). RESULTS: DC cocultures strongly 
      exhibited the production of TNF-alpha and IL-1 compared with other cultures, and 
      these cytokines were mainly produced by KCs, especially by activated KCs. Time 
      course studies revealed an increased production of TNF-alpha preceding the IL-1 
      production, suggesting that increased TNF-alpha levels could be involved in the 
      increase of IL-1 production. Leflunomide's active metabolite, A(771726), had 
      significantly inhibitory effect on TNF-alpha and IL-1 at protein and 
      transcription levels, and the reduced production of IL-1 by A(771726) was 
      associated with the inhibitory action of A(771726 ) on TNF-alpha. CONCLUSION: 
      Leflunomide can inhibit hepatocyte damage by inhibiting proinflammatory cytokine 
      release from KCs.
FAU - Yao, Hong-Wei
AU  - Yao HW
AD  - Zhejiang Respiratory Drugs Research Laboratory, State Drug Administration of 
      China, School of Medicine, Zhejiang University, Hangzhou, China.
FAU - Li, Jun
AU  - Li J
FAU - Chen, Ji-Qiang
AU  - Chen JQ
FAU - Xu, Shu-Yun
AU  - Xu SY
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - World J Gastroenterol
JT  - World journal of gastroenterology
JID - 100883448
RN  - 0 (Aniline Compounds)
RN  - 0 (Crotonates)
RN  - 0 (Hydroxybutyrates)
RN  - 0 (Immunosuppressive Agents)
RN  - 0 (Interleukin-1)
RN  - 0 (Isoxazoles)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (Nitriles)
RN  - 0 (Toluidines)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 1C058IKG3B (teriflunomide)
RN  - G162GK9U4W (Leflunomide)
SB  - IM
MH  - Aniline Compounds/pharmacology
MH  - Animals
MH  - Cell Communication/drug effects
MH  - Cells, Cultured
MH  - Crotonates
MH  - Hepatitis/immunology/metabolism/pathology
MH  - Hepatocytes/cytology/*immunology/metabolism
MH  - Hydroxybutyrates/pharmacology
MH  - Immunosuppressive Agents/*pharmacology
MH  - Interleukin-1/metabolism
MH  - Isoxazoles/*pharmacology
MH  - Kupffer Cells/cytology/*drug effects/*immunology
MH  - Leflunomide
MH  - Lipopolysaccharides/pharmacology
MH  - Male
MH  - Nitriles
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Toluidines
MH  - Tumor Necrosis Factor-alpha/metabolism
PMC - PMC4572763
EDAT- 2004/05/27 05:00
MHDA- 2004/07/20 05:00
PMCR- 2004/06/01
CRDT- 2004/05/27 05:00
PHST- 2004/05/27 05:00 [pubmed]
PHST- 2004/07/20 05:00 [medline]
PHST- 2004/05/27 05:00 [entrez]
PHST- 2004/06/01 00:00 [pmc-release]
AID - 10.3748/wjg.v10.i11.1608 [doi]
PST - ppublish
SO  - World J Gastroenterol. 2004 Jun 1;10(11):1608-11. doi: 10.3748/wjg.v10.i11.1608.