C/EBP β Mediates the Aberrant Inflammatory Response and Cell Cycle Arrest in Lps-stimulated Human Renal Tubular Epithelial Cells by Regulating NF-κB Pathway

Abstract

The main cause of sepsis-induced Acute kidney injury (AKI) is acute infection after surgery and subsequent progression. However, the mechanism by which AKI is caused and developed from sepsis are not completely known. Herein, we determined the role of CCAAT/enhancer-binding protein β (C/EBP β) in sepsis-induced AKI METHODS: C/EBP β expression was up or down-regulated in LPS-stimulated human renal tubular epithelial cells in vitro by recombinant adenoviruses or siRNA. Subsequent analyses included the test of TNF-α and IL-6 levels by ELISA, cell cycle assay by flow cytometry. C/EBP β was aberrantly expressed in renal tubular epithelial HK-2 cells exposed to LPS. C/EBP β overexpression significantly enhanced, but C/EBP β silencing obviously decreased the production and secretion of inflammatory cytokines TNF-α and IL-6 induced by LPS stimulus in HK-2 cells. And the cell cycle arrest of HK-2 cells induced by LPS was also enhanced after C/EBP β overexpression while attenuated after C/EBP β silencing. Consistent pattern of changes in Cyclin D1 and p21 expression were observed in LPS-stimulated HK-2 cells after C/EBP β silencing and C/EBP β overexpression. Additionally, the increased p-NF-κB levels induced by LPS were found to be obviously decreased after C/EBP β silencing in HK-2 cells. And the enhanced TNF-α and IL-6 secretion as well as cell cycle arrest by C/EBP β overexpression were blocked by BAY11-7082 inhibitor of NF-κB pathway. C/EBP β could mediate the LPS-induced aberrant inflammatory response and cell cycle arrest in tubular epithelial cells by NF-κB pathway.