Increased expression of interleukin-27 and its inhibitory effect on apoptosis in cisplatin-induced acute kidney injury / 上海交通大学学报（医学版）

ABSTRACT

Objective • To investigate the expression of interleukin-27 (IL-27) in cisplatin-induced acute kidney injury (AKI) and explore its inhibitory effect on apoptosis in AKI. Methods • C57BL/6 mice were randomly divided to control group and cisplatin group, in which mice were sacrificed at 24, 48 and 72 h after cisplatin administration. Blood urea nitrogen (BUN) and serum creatinine (Scr) levels were estimated. And the levels of mRNA for the IL-27 subunits, i.e. p28 and EBI3 in kidneys were determined by real-time PCR. As for in vitro experiments, after cisplatin incubation for 0.5, 1, 6, 12 and 24 h, HK-2 cells, a line of proximal tubular epithelial cells, were collected to assess the expression of IL-27 receptors (GP130 and WSX-1) at mRNA level. After that, HK-2 cells were treated with phosphate buffer saline or recombinant human IL-27 protein after cisplatin treatment, cell viability was detected by CCK-8, nuclear morphology was observed by Hoechst staining, and apoptosis related proteins including Bax, Bcl-2, and cleaved poly ADP-ribose polymerase (PARP) were estimated by Western blotting. Results • Compared with control group, BUN and Scr in cisplatin group significantly increased in a time-dependent manner after cisplatin injection. The mRNA levels of p28 and Ebi3 grew in injured kidneys, and their highest expressions were exhibited at 48 h after cisplatin injection. In HK-2 cells, GP130 and WSX-1 mRNA significantly increased at 1 h after cisplatin treatment but reduced to the basal level at 6, 12 and 24 h. IL-27 treatment significantly up-regulated cell viability and alleviated apoptosis and necrosis in cisplatin-treated HK-2 cells. In addition, IL-27 treatment inhibited the cleaved PARP and pro-apoptotic protein Bax, and upregulated antiapoptotic protein Bcl-2 in cisplatin-treated HK-2 cells. Conclusion • The expression of IL-27 increases in cisplatin-induced AKI, and it may protect against AKI by reducing cell apoptosis.