Disrupted NF- kappa B activation after partial hepatectomy does not impair hepatocyte proliferation in rats.
OBJECTIVE
To analyze the effects of NF- kappa B inhibition by antioxidant pyrrolidine dithiocarbamate (PDTC) or TNF inhibitor pentoxifylline (PTX) on liver regeneration after partial hepatectomy (PH).


METHODS
Saline, PDTC or PTX were injected 1 h before PH and rats were killed at 0.5 and 24 h after PH. Several control groups were used for comparison (injection control groups).


RESULTS
Compared to saline injected controls, NF- kappa B activation was absent 0.5 h after PH in rats treated with PDTC or PTX. At 24 h after PH, DNA synthesis and PCNA expression were identical in treated and control rats and thus occurred irrespectively of the status of NF- kappa B activation at 0.5 h. Signal transducer and activator of transcription 3 (Stat3) activation was observed already 0.5 h after PH in saline, PDTC or PTX group and was similar to Stat3 activation in response to injection without PH.


CONCLUSIONS
These data strongly suggest that (1) NF- kappa B p65/p50 DNA binding produced in response to PH is not a signal necessary to initiate the liver regeneration, (2) Stat3 activation is a stress response unrelated to the activation of NF- kappa B. In conclusion, NF- kappa B activation is not critically required for the process of liver regeneration after PH.
Laurent
Stéphanie
S
Department of Gastroenterology, St. Luc University Hospital, Av. Hippocrate 10, 1200 Brussels, Belgium.
Horsmans
Yves
Y
Stärkel
Peter
P
Leclercq
Isabelle
I
Sempoux
Christine
C
Lambotte
Luc
L
D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D006498:Hepatectomy; D022781:Hepatocytes / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D008115:Liver Regeneration / Q000187:drug effects / Q000502:physiology; D008297:Male; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism*; D010431:Pentoxifylline / Q000494:pharmacology; D011759:Pyrrolidines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D050796:STAT3 Transcription Factor / Q000378:metabolism; D013859:Thiocarbamates / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors
D016328:NF-kappa B; D011759:Pyrrolidines; D050796:STAT3 Transcription Factor; C494088:Stat3 protein, rat; D013859:Thiocarbamates; D014409:Tumor Necrosis Factor-alpha; C020972:pyrrolidine dithiocarbamic acid; D010431:Pentoxifylline