These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.


Pubmed for Handhelds

PUBMED FOR HANDHELDS

Search MEDLINE/PubMed

  • Title: C/EBPβ Acts Upstream of NF-κB P65 Subunit in Ox-LDL-Induced IL-1β Production by Macrophages.
    Author: Ma J, Liu C, Yang Y, Yu J, Yang J, Yu S, Zhang J, Huang L.
    Journal: Cell Physiol Biochem; 2018; 48(4):1605-1615. PubMed ID: 30071524.
    Abstract:
    BACKGROUND/AIMS: Interleukin-1β (IL-1β) is one of the critical inflammatory factors during atherogenesis. CCAAT/enhancer binding proteins β (C/EBPβ), a regulator of IL-1β production, recently been evidenced as a key player in the development of atherosclerosis. However, the mechanisms of how C/EBPβ regulates the production of IL-1β are unclear. In this study, we aimed to explore the role of C/EBPβ in regulating IL-1β production in macrophages after oxidized low-density lipoprotein (ox-LDL) exposure and the underlying mechanisms. METHODS: RAW264.7 macrophages were treated with 0, 25, 50 or 100 μg/ml ox-LDL for 12, 24 or 48 h. Small interfering RNAs were used to silence related proteins. The gene and protein expression levels were determined by quantitative real-time polymerase chain reaction or western blot (WB). IL-1β secretion was assessed by enzyme-linked immunosorbent assay. The cytoplasmic and nuclear proteins were evaluated by nuclear fractionation followed by WB. Localization of p65 was observed by immunofluorescence. The binding activity of p65 to IL-1β was tested by dual-luciferase reporter assay. RESULTS: Ox-LDL increased IL-1β production, accompanied with increasing C/EBPβ and p65 expression in a dose- and time-dependent manner. Moreover, C/EBPβ deficiency in macrophages blocked ox-LDL-induced increases in IL-1β expression, maturation as well as p65 activation. However, p65 deficiency inhibited the increase in IL-1β production, but not C/EBPβ expression. Dual-luciferase reporter results showed that overexpression of C/EBPβ significantly enhanced binding activity of p65 to IL-1β promoter. In addition, C/EBP 1β deficiency in macrophages abolished the ox-LDL-induced gene transcription increases of IL-1β, IL-6, p65 and caspase-1. CONCLUSIONS: Our results demonstrate that C/EBPβ acts upstream of NF-κB p65 subunit in ox-LDL-induced IL-1β production in macrophages and may regulate IL-1β maturation by promoting caspase-1. C/EBPβ may be a promising candidate for the prevention and treatment of atherosclerosis.
    [Abstract] [Full Text] [Related] [New Search]