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Prediction of Novel Genes Associated with Negative Regulators of Toll-like Receptors-Induced Inflammation Based on Endotoxin Tolerance

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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.

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Acknowledgments

This study was supported by the National Nature Science Foundation of China (No. 30872221) and Major Project in Key Area of Guangdong Province No. (2005)162.

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Authors and Affiliations

  1. Institute of Genomic Medicine Research, College of Pharmacy, Jinan University, Guangzhou, 510632, People’s Republic of China

    Yan Yang, Hanxiao Sun, Xuemei Mo, Yi Liu, Hongwei Jia, Xiuying Li, Guang Zhang & Qin Li

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  1. Yan Yang
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  2. Hanxiao Sun
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Correspondence to Hanxiao Sun.

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Yang, Y., Sun, H., Mo, X. et al. Prediction of Novel Genes Associated with Negative Regulators of Toll-like Receptors-Induced Inflammation Based on Endotoxin Tolerance. Inflammation 35, 1889–1899 (2012). https://doi.org/10.1007/s10753-012-9511-0

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