TREM-1 promoted apoptosis and inhibited autophagy in LPS-treated HK-2 cells through the NF-κB pathway.
Triggering receptor expressed by myeloid cells (TREM-1) is an amplifier of inflammatory responses triggered by bacterial or fungal infection. Soluble TREM-1 (sTREM-1) expression was found to be upregulated in sepsis-associated acute kidney injury (SA-AKI) and predicted to be a potential biomarker. However, the mechanism remains unclear. The human kidney-2 (HK-2) cell line was treated with lipopolysaccharide (LPS) and used to examine the potential roles of TREM-1 in apoptosis and autophagy. A cell viability assay was employed to assess the number of viable cells and as a measure of the proliferative index. The concentrations of sTREM-1, interleukin (IL)-1β, tumor necrosis factor-α (TNFα) and IL-6 in cell-free culture supernatants were measured by enzyme-linked immunosorbent assay (ELISA). Western blot analysis was performed to analyze apoptosis, autophagy and the relevant signaling pathways. The results suggested that TREM-1 overexpression after LPS treatment decreased proliferation and increased apoptosis. The concentrations of sTREM-1, IL-1β, TNFα and IL-6 in cell-free culture supernatants were increased in the TREM-1 overexpression group after LPS treatment. Expression of the antiapoptotic gene Bcl-2 was downregulated in the TREM-1 overexpression group, while that of the proapoptotic genes Bax, cleaved caspase-3 and cleaved caspase-9 was upregulated. Overexpression of TREM-1 downregulated expression of the autophagy genes Beclin-1, Atg-5 and LC3b and increased the gene expression of p62, which inhibits autophagy. Conversely, treatment with TREM-1-specific shRNA had the opposite effects. The nuclear factor-κB (NF-κB) signaling pathway (P-p65/p65 and P-IκBα/IκBα) in LPS-induced HK-2 cells was regulated by TREM-1. In summary, TREM-1 promoted apoptosis and inhibited autophagy in HK-2 cells in the context of LPS exposure potentially through the NF-κB pathway.
['Pan|Pan|P|', 'Liu|Xudong|X|', 'Wu|LingLing|L|', 'Li|Xiaogang|X|', 'Wang|Kaifei|K|', 'Wang|Xiaoting|X|', 'Zhou|Xiang|X|', 'Long|Yun|Y|', 'Liu|Dawei|D|', 'Xie|Lixin|L|', 'Su|Longxiang|L|']
D058186:Acute Kidney Injury D017209:Apoptosis D001343:Autophagy D002460:Cell Line D004847:Epithelial Cells D006801:Humans D007668:Kidney D008070:Lipopolysaccharides D016328:NF-kappa B D034741:RNA, Small Interfering D018805:Sepsis D015398:Signal Transduction D000073871:Triggering Receptor Expressed on Myeloid Cells-1
TREM-1 Apoptosis Autophagy AKI NF-κB signaling pathway Sepsis