Interleukin-15 increases hepatic regenerative activity

• DOI: 10.1016/j.jhep.2006.04.008
• Publication Date: 2006-05-23T20:49:47Z
• Authors: Ayako Suzuki; Shannon McCall; Steve S. Choi; Jason K. Sicklick; Jiawen Huang; Yi Qi; Marzena Zdanowicz; Terese Camp; Yin-Xiong Li; Anna Mae Diehl
• Keywords: Liver Regeneration; Hepatic stellate cell

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.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.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.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.