Sex-dependent differences in inflammatory responses during liver regeneration in a murine model of acute liver injury

A sexual dimorphism in liver inflammation and repair was previously demonstrated. Its cellular dissection in the course of acute liver injury (ALI) was explored. BALB/c mice were treated with carbon tetrachloride (CCl4) by intraperitoneal injection and sacrificed after 3, 5 and 8 days. Histological and hepatic cell population analyses were performed. The correlation between androgen receptor (AR) expression and liver recruited inflammatory cells was investigated by treatment with the AR antagonist flutamide. Additionally, patients with a diagnosis of Drug Induced Liver Injury (DILI) were included in the study, with a particular focus on gender dimorphism in circulating monocytes. A delayed resolution of necrotic damage and a higher expression of pro-inflammatory cytokines were apparent in male mice along with a slower recruitment of inflammatory monocytes. F4/80+CD11b+ macrophages and CD11bhighGr-1high monocytes expressed AR and were recruited later in male compared to female livers after CCl4 treatment. Moreover, CD11bhighAR+Gr-1high recruitment was negatively modulated by flutamide in males. Analysis of DILI patients showed overall a significant reduction of circulating mature monocytes compared to healthy subjects. More interestingly, male patients had higher numbers of immature monocytes compared to female patients. A stronger cytotoxic tissue response was correlated with an impaired recruitment of CD11bhighAR+Gr-1high cells and F4/80+CD11b+ macrophages in the early ...

Source: Clinical Science - December 11, 2017 Category: Biomedical Science Authors: Bizzaro, D., Crescenzi, M., Di Liddo, R., Arcidiacono, D., Cappon, A., Bertalot, T., Amodio, V., Tasso, A., Stefani, A., Bertazzo, V., Germani, G., Frasson, C., Basso, G., Parnigotto, P., Alison, M. R., Burra, P., Conconi, M. T., Russo, F. P. Tags: PublishAheadOfPrint Source Type: research