IL-1R1 deficiency impairs liver regeneration after 2/3 partial hepatectomy in aged mice

Authors: DEMING LI, ZE WANG, CHUNYAN ZHANG, CUNSHUAN XU

Abstract: Inflammation has a dual effect: it can protect the body and destroy tissue and cell as well. The purpose of this experiment was to determine the role of IL-1R1 in liver regeneration (LR) after partial hepatectomy (PH) in aged mice. The wild-type (WT, n = 36) and the IL-1R1 knockout (KO, n = 36) 24-month-old C57BL/6J mice underwent two-thirds PH; 33 WT mice underwent sham operation. Liver coefficient was calculated by liver/body weight. The mRNA and protein expressions of genes were evaluated by quantitative realtime polymerase chain reaction (qRT-PCR) and Western blotting methods, respectively. Compared with WT mice, liver coefficient was lower in the IL-1R1 KO aged mice at 168 and 192 h (p = 0.039 and p = 0.027). The mRNA transcription of inflammation-related genes and cell cycle-associated genes decreased or delayed. The protein expressions of proliferation-related marker PCNA and proliferationassociated signaling pathway components JNK1, NF-κB and STAT3 reduced or retarded. There was stronger activation of proapoptotic proteins caspase-3, caspase-8 and BAX in the IL-1R1 KO mice at different time points (p < 0.05 or p < 0.01). IL-1R1 KO reduced inflammation and caused impaired liver regeneration after 2/3 partial hepatectomy in aged mice. Maintaining proper inflammation may contribute to regeneration after liver partly surgical resection in the elderly.

Keywords: Aged mice, IL-1R1, inflammation, liver resection, regeneration

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