IL-6-mediated inflammation promotes cardiomyocyte proliferation in neonatal mice

XIAO Fei; JIANG Zhihui; FENG Guangzhi; CHEN Zhen; DING Guobin

doi:10.13431/j.cnki.immunol.j.20170055

Abstract：To explore the role and mechanisms of IL-6-mediated inflammation in cardiomyocyte proliferation in mice,neonatal 1 d mice were recruited and divided into two groups:sham operation group and model group.The mice in model group were undergone low temperature anesthesia,then the apex of the heart was removed after thoracotomy;the sham operation group was also performed low temperature anesthesia,thoracotomy and suture process,except the apical resection.Mice was sacrificed at 1 d,3 d,7 d and 3 weeks post-surgery respectively,and HE staining was conducted to evaluate the condition of cardiac repair in the two groups.QPCR analysis was used to detect the expression of proliferation related genes and il-6,il-1β and icam1;the expression levels of serum I L-6,TNF-α and IL-1β were checked by ELISA kit;The expression levels of IL-6 downstream targets Akt,Akt (S473),Stat3,Stat3 (T705),and the phosphatase PP2A were investigated by Western blotting.Data showed that the neonatal heart of model group was completely regenerated 7 days after the operation,the regenerated apex restored complete structure.The cardiomyocyte proliferation related genes were significantly increased in the cardiac regeneration process.The transcriptional levels of il-6,il-lβ and icaml were enhanced in the early course of regeneration.IL-6,TNF-α and IL-1β was drastically incresed,in addition,the phosphorylation levels of IL-6 downstream targets Akt and Stat3 were sharply increased during the process of the cardiac regeneration.PP2A and its subunit B56α were significantly decreased at 1 d and 3d post-surgery and restored to normal levels at week 3.Taken together,the newborn mice have the ability to regenerate the heart completely.And IL-6-mediated early acute inflammation is critical in cardiomyocyte proliferation after the cardiac injury.