CONICET | Buscador de Institutos y Recursos Humanos

MyD88 is involved in the Toll-like receptor and IL-1 receptor signalingpathway in the innate immune response. It is known that inflammationis an important component of tumorigenesis. We statethat the signaling through MyD88 has a key role in liver cancer developmentin mice. Adult C57BL/6 wild-type (WT) and MyD88-/- mice(23-25 g) were subject to a model of early liver cancer development.This was induced by administration of 2 i.p. doses of diethylnitrosamine(75 mg/kg bw) 2 weeks apart. One week after the last injection,mice received 20 mg/kg bw of 2-acetylaminofluorene by gastricprobe 3 days a week for 3 weeks. All studies were performed beforethe initiation of the treatment and showed no difference betweengenotypes. After the hepatocarcinogenic treatment, MyD88-/- miceshowed lower body weight but higher liver weight than WT mice.We confirmed the complete absence of liver MyD88 protein expressionby immunoblotting, as well as MyD88 mRNA expression, whenevaluated by qPCR. Liver histology analysis showed scatter alterationson hepatocyte architecture, with accumulation of cytosoliclipid droplets (+23%) and increased inflammatory infiltration (+45%)in MyD88-/- mice compared to WT mice. Hepatic enzymes aspartateaminotransferase (AST) and alanine aminotransferase (ALT) wereslightly increased (+15%, and +12%, respectively) in plasma ofMyD88-/- mice compared to WT mice, indicating a mild liver damage.Then, we evaluated proliferation and apoptosis by immunoblotting.We found that MyD88-/- mice presented with increased protein expressionof proliferation cell nuclear antigen (PCNA) (+35%) anddecreased levels of caspase 3 (-31%) in total liver homogenates.These studies represent the first steps in the evaluation of the role ofMyD88 in liver cancer development, and demonstrate that MyD88 isparticipating in preventing chemical hepatocarcinogenesis; exposing,once again, the tight relationship between the immune systemand the de development of cancer