Impaired liver regeneration is associated with reduced cyclin B1 in natural killer T cell-deficient mice.
BACKGROUND
It has been shown that the proportion of natural killer T cells is markedly elevated during liver regeneration and their activation under different conditions can modulate this process. As natural killer T cells and liver injury are central in liver regeneration, elucidating their role is important.


METHODS
The aim of the current study is to explore the role of natural killer T cells in impaired liver regeneration. Concanvalin A was injected 4 days before partial hepatectomy to natural killer T cells- deficient mice or to anti CD1d1-treated mice. Ki-67 and proliferating cell nuclear antigen were used to measure hepatocytes proliferation. Expression of hepatic cyclin B1 and proliferating cell nuclear antigen were evaluated by Western Blot and liver injury was assessed by ALT and histology.


RESULTS
Natural killer T cells- deficient or mice injected with anti CD1d antibodies exhibited reduced liver regeneration. These mice were considerably resistant to ConA-induced liver injury. In the absence of NKT cells hepatic proliferating cell nuclear antigen and cyclin B1 decreased in mice injected with Concanvalin A before partial hepatectomy. This was accompanied with reduced serum interleukin-6 levels.


CONCLUSIONS
Natural killer T cells play an important role in liver regeneration, which is associated with cyclin B1 and interleukin-6.
Liver Unit, Hebrew University-Hadassah Medical Center, Jerusalem, Israel. amib@szmc.org.il.
Ami
A
Ben Ya'acov
Liver Unit, Hebrew University-Hadassah Medical Center, Jerusalem, Israel.
Hadar
H
Meir
Liver Unit, Hebrew University-Hadassah Medical Center, Jerusalem, Israel.
Lydia
L
Zolotaryova
Liver Unit, Hebrew University-Hadassah Medical Center, Jerusalem, Israel.
Yaron
Y
Ilan
Department of Pediatrics, Hebrew University-Hadassah Medical Center, Jerusalem, Israel.
Eyal
E
Shteyer
D000410:Alanine Transaminase / Q000378:metabolism; D000818:Animals; D055610:Antigens, CD1d / Q000235:genetics; D015153:Blotting, Western; D049109:Cell Proliferation / Q000187:drug effects / Q000235:genetics; D003208:Concanavalin A / Q000633:toxicity; D056744:Cyclin B1 / Q000187:drug effects / Q000378:metabolism*; D004591:Electrophoresis, Polyacrylamide Gel; D006498:Hepatectomy; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism*; D015850:Interleukin-6 / Q000378:metabolism*; D008099:Liver / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D008115:Liver Regeneration / Q000187:drug effects / Q000235:genetics*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008934:Mitogens / Q000633:toxicity; D055611:Natural Killer T-Cells; D018809:Proliferating Cell Nuclear Antigen / Q000187:drug effects / Q000378:metabolism*
D055610:Antigens, CD1d; C584692:CD1d antigen, mouse; C534700:Ccnb1 protein, mouse; D056744:Cyclin B1; D015850:Interleukin-6; D008934:Mitogens; D018809:Proliferating Cell Nuclear Antigen; C577686:interleukin-6, mouse; D003208:Concanavalin A; D000410:Alanine Transaminase
CD1d; CyclinB1; Interleukin-6; Liver regeneration; NKT cells