title: Prediction of novel genes associated with negative regulators of toll-like receptors-induced inflammation based on endotoxin tolerance.
abstract: Prior exposure of innate immune cells to lipopolysaccharide (LPS) has caused them to be refractory to further endotoxin stimulation, also termed endotoxin tolerance (ET). Bacterial LPS signals through Toll-like receptor (TLR) 4, which was thought to enable the innate immune system to deal with invasive pathogens and to restrain systemic inflammation efficiently. We established a robust model of ET and determined the level of TNF-α and IL-6 in cultured human monocytes. Then, microarray assay was applied to assess gene expression in this model. The results showed that 356 non-tolerizable genes were differentially expressed at a high level in tolerant monocytes. The genes selected were classified into several categories based on gene ontology (GO) and KEGG pathway database. And then literature annotations, protein-protein interaction (PPI) network, and functional consistency were applied to analyze the non-tolerizable genes. Finally, the microarray results were verified by quantitative real-time PCR of seven representative genes, including the two candidate genes, Spry2 and Smurf2, which were supposed to play a critical role in TLRs-induced inflammation based on literature retrieval. Our results would provide useful information for further analysis of regulating TLRs-induced inflammation, and would facilitate the study of associated mechanisms.
authors: Institute of Genomic Medicine Research, College of Pharmacy, Jinan University, Guangzhou 510632, People's Republic of China.
authors: Yan
authors: Y
authors: Yang
authors: Hanxiao
authors: H
authors: Sun
authors: Xuemei
authors: X
authors: Mo
authors: Yi
authors: Y
authors: Liu
authors: Hongwei
authors: H
authors: Jia
authors: Xiuying
authors: X
authors: Li
authors: Guang
authors: G
authors: Zhang
authors: Qin
authors: Q
authors: Li
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D002478:Cells, Cultured; D004731:Endotoxins / Q000276:immunology*; D015870:Gene Expression; D020869:Gene Expression Profiling; D006801:Humans; D007249:Inflammation / Q000235:genetics*; D015850:Interleukin-6 / Q000032:analysis; D047908:Intracellular Signaling Peptides and Proteins; D007963:Leukocytes, Mononuclear / Q000276:immunology*; D008565:Membrane Proteins / Q000235:genetics; D017346:Protein Serine-Threonine Kinases; D015398:Signal Transduction / Q000276:immunology; D051197:Toll-Like Receptor 4 / Q000235:genetics*; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis; D044767:Ubiquitin-Protein Ligases / Q000235:genetics
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D004731:Endotoxins; D015850:Interleukin-6; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha; C533325:Smurf2 protein, mouse; D044767:Ubiquitin-Protein Ligases; D017346:Protein Serine-Threonine Kinases; C118389:Spry2 protein, mouse