PMID- 16307221
OWN - NLM
STAT- MEDLINE
DCOM- 20060105
LR  - 20161124
IS  - 1023-3830 (Print)
IS  - 1023-3830 (Linking)
VI  - 54
IP  - 11
DP  - 2005 Nov
TI  - Effect and mechanisms of FR167653, a dual inhibitor of TNF-alpha and IL-1, on BCG 
      plus LPS induced-liver injury.
PG  - 471-7
AB  - OBJECTIVE: To investigate the effect of FR167653, a dual inhibitor of tumor 
      necrosis factor-alpha (TNF-alpha) and interleukin-1 (IL-1), on Bacillus 
      Calmette-Guerin (BCG) plus lipopolysaccharide (LPS) induced-liver injury and its 
      mechanisms. MATERIAL AND METHODS: Mouse liver injury was established by tail vein 
      injection of 2.5 mg BCG, and 10 d later with 10 microg LPS. The alanine 
      aminotransferase (ALT) and aspartate aminotransferase (AST) were assayed by 
      spectrophotometry. Liver samples were stained with hematoxylin and eosin. Rat 
      hepatocytes (HCs) and Kupffer cells (KCs) were isolated by collagenase IV and 
      pronase perfusion, and purified by density gradient separation. TNF-alpha and 
      IL-1 concentrations were measured with ELISA. TNF-alpha and IL-1 mRNA in KCs was 
      analyzed with RT-PCR. RESULTS: FR167653 significantly decreased the elevated 
      transaminase (ALT, AST) activity in serum of liver injured mice. Meanwhile, the 
      degree of inflammatory cell infiltration and liver cell necrosis was also 
      ameliorated. TNF-alpha and IL-1 production by KCs stimulated with LPS was 
      significantly inhibited by FR167653. RT-PCR analysis demonstrated that FR167653 
      also reduced the augmented expression of TNF-alpha and IL-1 mRNA in KCs. However, 
      FR167653 up to 10 micromol/L did not have a toxic effect on KC viability. In 
      addition, FR167653 alleviated the HC injury induced by LPS pre-treated Kupffer 
      cell-conditioned medium (KCCM). Addition of anti-IL-1 and anti-TNF-alpha MAbs 
      significantly decreased the ALT level released from HCs incubated with LPS or 
      FR167653 pre-treated KCCM. CONCLUSIONS: TNF-alpha and IL-1 released from 
      activated KCs were involved in BCG plus LPS induced liver injury. FR167653 
      significantly attenuated hepatocyte injury via inhibition of TNF-alpha and IL-1 
      released from activated KCs.
FAU - Yao, H W
AU  - Yao HW
AD  - Department of Pharmacology, School of Medicine, Zhejiang University, Hangzhou, 
      310031, China. yhgwei@hotmail.com
FAU - Yue, L
AU  - Yue L
LA  - eng
PT  - Journal Article
PL  - Switzerland
TA  - Inflamm Res
JT  - Inflammation research : official journal of the European Histamine Research 
      Society ... [et al.]
JID - 9508160
RN  - 0 (Anti-Inflammatory Agents, Non-Steroidal)
RN  - 0 (Culture Media, Conditioned)
RN  - 0 (FR 167653)
RN  - 0 (Interleukin-1)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (Pyrazoles)
RN  - 0 (Pyridines)
RN  - 0 (Tumor Necrosis Factor-alpha)
SB  - IM
MH  - Animals
MH  - Anti-Inflammatory Agents, Non-Steroidal/*pharmacology
MH  - Chemical and Drug Induced Liver Injury/pathology/*prevention & control
MH  - Culture Media, Conditioned
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Interleukin-1/*antagonists & inhibitors
MH  - Kupffer Cells/metabolism
MH  - Lipopolysaccharides/*toxicity
MH  - Liver/enzymology/pathology
MH  - Liver Function Tests
MH  - Male
MH  - Mice
MH  - *Mycobacterium bovis
MH  - Pyrazoles/*pharmacology
MH  - Pyridines/*pharmacology
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Tuberculosis/*microbiology
MH  - Tumor Necrosis Factor-alpha/*antagonists & inhibitors
EDAT- 2005/11/25 09:00
MHDA- 2006/01/06 09:00
CRDT- 2005/11/25 09:00
PHST- 2005/11/25 09:00 [pubmed]
PHST- 2006/01/06 09:00 [medline]
PHST- 2005/11/25 09:00 [entrez]
AID - 10.1007/s00011-005-1381-6 [doi]
PST - ppublish
SO  - Inflamm Res. 2005 Nov;54(11):471-7. doi: 10.1007/s00011-005-1381-6.