期刊
INTERNATIONAL JOURNAL OF MEDICAL SCIENCES
卷 18, 期 1, 页码 8-17出版社
IVYSPRING INT PUBL
DOI: 10.7150/ijms.50893
关键词
Sepsis; AKI; TREM-1; Apoptosis; Autophagy; NF-kappa B signaling pathway
资金
- Beijing Municipal Natural Science Foundation [7192163]
- Beijing Nova Program from Beijing Municipal Science & Technology Commission [Z201100006820126]
- State Key Laboratory of Kidney Diseases, Chinese People's Liberation Army General Hospital [KF-19-08]
- National Science Foundation for Young Scientists of China [81901935]
- Capital Foundation of Medical Development [2016-1-5015]
- China National Key Reseach Program [2018ZX09201013]
TREM-1 acts as an amplifier of inflammatory responses triggered by bacterial or fungal infection. It promotes apoptosis and inhibits autophagy in HK-2 cells exposed to LPS potentially through the NF-kappa B 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)-1 beta, tumor necrosis factor-alpha (TNF alpha) 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-1 beta, TNF alpha 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-kappa B (NF-kappa B) signaling pathway (P-p65/p65 and P-I kappa B alpha/I kappa B alpha) 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-kappa B pathway.
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