Interleukin-15 increases hepatic regenerative activity.
OBJECTIVE
Interleukin-15 (IL-15) is expressed in many organs. It generally inhibits apoptosis and increases cellular proliferation and differentiation. However, IL-15's roles in liver are unknown. We aimed to determine if IL-15 influences hepatic integrity and regenerative activity.


METHODS
Expression of IL-15 and its receptors was evaluated in several liver injury models, primary hepatocytes, and two liver cell lines. Effects of IL-15 on viability, proliferation, and apoptosis were assessed in cultured liver cells, and also in the livers of healthy mice.


RESULTS
IL-15 and its receptors are expressed constitutively in healthy livers, and ligand expression is induced in injured livers. Cultured primary hepatocytes and liver cell lines express IL-15 and its receptors. Administration of IL-15 has minimal effects on cultured liver cells, but significantly up-regulates oval cell accumulation, cyclin mRNA expression, and mature hepatocyte replication in healthy mice. These effects are associated with focal hepatic inflammation and increased expression of TNF-alpha and IFN-gamma, but not with increased cell death or aminotransferase release.


CONCLUSIONS
IL-15 expression increases during liver injury and IL-15 treatment induces a wound healing-type response in healthy adult mice. These findings suggest that IL-15 may contribute to regenerative activity in damaged liver.
Suzuki
Ayako
A
Division of Gastroenterology and Department of Medicine, Duke University Medical Center, Durham, NC, USA.
McCall
Shannon
S
Choi
Steve S
SS
Sicklick
Jason K
JK
Huang
Jiawen
J
Qi
Yi
Y
Zdanowicz
Marzena
M
Camp
Terese
T
Li
Yin-Xiong
YX
Diehl
Anna Mae
AM
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D005786:Gene Expression Regulation / Q000235:genetics; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism; D007249:Inflammation; D007371:Interferon-gamma / Q000235:genetics / Q000378:metabolism; D019409:Interleukin-15 / Q000235:genetics* / Q000378:metabolism* / Q000494:pharmacology; D008099:Liver / Q000187:drug effects / Q000293:injuries / Q000378:metabolism* / Q000473:pathology; D008115:Liver Regeneration / Q000235:genetics* / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008820:Mice, Obese; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D053647:Receptors, Interleukin-15 / Q000235:genetics / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism; D014945:Wound Healing
D019409:Interleukin-15; D012333:RNA, Messenger; D053647:Receptors, Interleukin-15; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma