The role of Toll-like receptors in liver regeneration after partial hepatectomy.
Spyridon Dritsas, Maximos Frountzas, Dimitrios Schizas, Francesk Mulita, Michalis Katsimpoulas, Paraskevas Gkolfakis, Irene Lidoriki, Ioannis Karavokyros, Elias Liolis, Evangelos Missiakos, Theodore Liakakos, Alkistis Kapelouzou
Abstract
Open AccessIntroduction: Toll-like receptors (TLRs) play a key role in activating the immune system response after liver injury. Aim: This experimental study aimed to investigate the expression of TLRs and their connecting signaling molecules in liver regeneration. Material and methods: Eighty C57BL/6J mice were divided into eight equal groups: four groups underwent partial hepatectomy (liver resection, LR), and four groups underwent an abdominal incision without hepatectomy (sham, Sh). One group of each type was sacrificed at 12 h (LR12 and Sh12), 24 h (LR24 and Sh24), 36 h (LR36 and Sh36), and 168 h (LR168 and Sh168). Histological and immunohistochemical analyses, blood tests, and quantitative real-time polymerase chain reaction (qRT-PCR) were performed. Results: The qRT-PCR tests indicated significant differences in all immune response proteins (TLR1, TLR2, TLR6, IRAK4, TIRAP, NF-kB, MYD88) between all LR and Sh groups. A progressive increase in the expression of TLRs was observed in the first three pairs, with stabilization of their expression in the last group. Histological examination of liver specimens revealed regeneration of liver tissue in the LR groups. Immunohistochemical analysis revealed increased expression of signaling proteins (TLR1, TLR2, MYD88, IRAK4, TIRAP, NF-kB) in the LR groups as compared to the control groups. White blood, red blood cell count and liver function tests were significantly different between LR and Sh groups. Conclusions: TLR expression was significantly higher in mice that underwent partial hepatectomy than the controls. Further research is required to investigate their potential as therapeutic targets in the management of acute or chronic liver failure after partial hepatectomy.