DNA and cell biology
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DNA and cell biology · Dec 2019
Anti-Inflammatory Activity of Adenosine 5'-Trisphosphate in Lipopolysaccharide-Stimulated Human Umbilical Vein Endothelial Cells Through Negative Regulation of Toll-Like Receptor MyD88 Signaling.
Activation of TLR4-MyD88-NF-κB signaling by lipopolysaccharide (LPS) evokes a proinflammatory immune response, and plays a pivotal role in initiation and progression of atherosclerosis (AS). ATP (adenosine 5'-trisphosphate), a powerful extracellular signal transduction molecule, functions to regulate immune inflammatory responses depending on the type of P2 receptors and cell lines. In this study, we first performed RT-PCR to detect the mRNA expression of monocyte chemoattractant protein-1 (MCP-1), IL-8, and IL-1β induced by different concentrations of LPS in human umbilical vein endothelial cells (HUVECs). ⋯ ATP at low concentrations also downregulated the mRNA expression of TLR4, CD14, and MyD88 and inhibited LPS-induced phosphorylation of p65. Furthermore, Suramin, a nonspecific P2Y receptor antagonist, did not attenuate the inhibition of ATP on LPS-induced IL-1β and MCP-1 expression. Taking this together, low concentration ATP inhibited LPS-induced inflammation in HUVECs by negatively regulating TLR4-MyD88 signaling, and P2Y receptors were not involved in this process, which might provide new ideas for prevention and treatment of inflammatory diseases such as AS.
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DNA and cell biology · Dec 2019
Identification of DDX58 and CXCL10 as Potential Biomarkers in Acute Respiratory Distress Syndrome.
Acute respiratory distress syndrome (ARDS) is a devastating condition of acute inflammatory lung injury and causes high morbidity and mortality. Therefore, investigations on the effective biomarkers will be significant for the understanding of ARDS. In our research, the gene expression profiles of 27 samples from ARDS patients (n = 18) and healthy controls (n = 9) were analyzed and eight gene co-expression modules were identified by constructing weighted gene co-expression network. The correlation analysis of modules with phenotypes showed that genes in the yellow and black modules, which were significantly enriched in the ARDS-related pathways, such as TNF signaling pathway, Toll-like receptor signaling pathway, and NF-kappa B signaling pathway, were associated with the phenotype "time postinfection." Genes DDX58 and CXCL10, which were highly expressed after infection and significantly enriched in ARDS-related pathways, presented high score in protein-protein interaction analysis, indicating that they may be associated with ARDS and providing novel biomarkers for its diagnosis, treatment, and surveillance.