[Intracellular signal transduction pathways of IL-1 beta-induced cytotoxicity on primary cultured rat hepatocytes].
OBJECTIVE
To investigate the intracellular signal transduction pathways of IL-1 beta-induced cytotoxicity on primary cultured rat hepatocytes.


METHODS
All studies were based on primary cultured hepatocytes from male Wistar strain rats (5 to 7 weeks old, 170 to 230 g). The activity of lactose dehydrogenase (LDH) was detected by colormetric assay. JNK and p38 kinase were analyzed by Western blot assay. The AP-1 activity was evaluated by electrophoretic mobility shift assay.


RESULTS
IL-1 beta significantly increased LDH release. LDH activity in group IL-1 beta and controls was 21.9% +/- 3.6% and 11.0% +/- 1.8% respectively, P < 0.01). IL-1 beta induced cytotoxicity via activating JNK pathway and transcription factor AP-1 and the simultaneous activation of p38 kinase pathway negatively regulated this process.


CONCLUSIONS
IL-1 beta induces cytotoxicity in primary cultured rat hepatocytes via activating JNK pathway and transcription factor AP-1.
Zhang
Z
Z
Department of General Surgery, Beijing Friendship Hospital, Capital University of Medical Sciences, Beijing 100050, China.
Wang
Y
Y
D000818:Animals; D002478:Cells, Cultured; D022781:Hepatocytes / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology*; D048031:JNK Mitogen-Activated Protein Kinases; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008297:Male; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects; D018808:Transcription Factor AP-1 / Q000378:metabolism*; D048051:p38 Mitogen-Activated Protein Kinases
D007375:Interleukin-1; D011994:Recombinant Proteins; D018808:Transcription Factor AP-1; D007770:L-Lactate Dehydrogenase; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases