CCAAT/enhancer-binding protein β (C/EBPβ) expression regulates oxidized low-density lipoprotein (ox-LDL) -induced inflammation in macrophages

Jun MA, San-jiu YU, Hua-li KANG, Meng-yang DENG, Lan HUANG
2018 Medical Journal of Chinese People's Liberation Army  
Objective To investigate the role of CCAAT/enhancer binding protein β (C/EBPβ) in the production of IL- 1β induced by oxidized low-density lipoprotein (ox-LDL) in macrophages. Methods Macrophages RAW264.7 cell line treated with 0, 25, 50 and 100μg/ml ox-LDL for 12, 24 and 48h, 0μg/ml ox-LDL at each time point served as a control group, and then 50μg/ml ox-LDL treated for 24h was selected for subsequent experiments. Small interfering RNAs (siRNAs) were used to silence C/EBPβ as well as
more » ... s well as caspase-1. The gene and protein expression levels were determined by quantitative real-time polymerase chain reaction (qPCR) and Western blotting, respectively. ELISA was used to detect the secretion of IL-1β in the supernatant. Results Ox-LDL increased the expressions of C/EBPβ gene and protein in a dose- and time-dependent manner, wherein the expression of C/EBPβ protein was up-regulated obviously in an average up-regulation of 57% after 50μg/ml ox-LDL treatment for 24 hours (P<0.01). Besides, ox-LDL markedly increased the expressions of caspase-1, pro-IL-1β and cleaved-IL-1β (P<0.05). Moreover, C/EBPβ knocked-down may inhibit the ox-LDL-induced increase of caspase-1, pro-IL-1β, cleaved-IL-1β expression and IL-1β secretion in an average inhibition of about 34%, 36%, 54% and 53%, respectively (P<0.05). However, caspase-1 deficiency may only block the cleaved-IL-1β expression and IL-1β secretion (P<0.05). Conclusions C/EBPβ plays a critical role in production of IL- 1β induced by ox-LDL in macrophages, and regulates the maturation of pro-IL-1β by affecting the expression of caspase-1. C/EBPβ is expected to become an important target in prevention and treatment of atherosclerosis. DOI: 10.11855/j.issn.0577-7402.2018.05.13
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