PMID- 22995314 OWN - NLM STAT- MEDLINE DCOM- 20130325 LR - 20121123 IS - 1090-2104 (Electronic) IS - 0006-291X (Linking) VI - 428 IP - 3 DP - 2012 Nov 23 TI - Role of RNA-binding protein tristetraprolin in tumor necrosis factor-alpha mediated gene expression. PG - 327-32 LID - S0006-291X(12)01773-1 [pii] LID - 10.1016/j.bbrc.2012.09.033 [doi] AB - Tumor necrosis factor-alpha (TNF-alpha) plays an important role in the pathogenesis of inflammatory diseases. Excessive TNF-alpha expression induces tristetraprolin (TTP), an RNA-binding protein that regulates mRNA degradation, which in turn downregulates TNF and its downstream genes, thus resulting in anti-inflammatory effects. In order to better understand the TNF-alpha mediated molecular pathways in inflammatory diseases, embryonic fibroblast (MEF) cell lines derived from TTP-deficient (KO) or wild type (WT) mice were treated with TNF-alpha and gene expression differences between two cell lines were compared by a microarray essay of 9224 genes. We found that TTP-KO cells had higher expression levels of pro-inflammatory genes than TTP-WT cells, and inflammatory genes were differentially regulated by TNF-alpha between TTP-KO and TTP-WT cells. Through a study of 2-dimentional gene set matrix analysis, we also found the genes upregulated by TNF-alpha in TTP KO cells were correlated with the pathologic phenotypes in inflammation, joint, or bone diseases. Our study provided a detailed genetic roadmap for further understanding the regulatory effect of TTP in inflammatory pathways related to human diseases. CI - Copyright (c) 2012 Elsevier Inc. All rights reserved. FAU - Chen, Xia AU - Chen X AD - Urology Department, Minhang District Central Hospital, Shanghai, China. FAU - Wei, Ziran AU - Wei Z FAU - Wang, Weimin AU - Wang W FAU - Yan, Ronlin AU - Yan R FAU - Xu, Xudong AU - Xu X FAU - Cai, Qingping AU - Cai Q LA - eng PT - Journal Article DEP - 20120917 PL - United States TA - Biochem Biophys Res Commun JT - Biochemical and biophysical research communications JID - 0372516 RN - 0 (RNA-Binding Proteins) RN - 0 (Tristetraprolin) RN - 0 (Tumor Necrosis Factor-alpha) RN - 0 (Zfp36 protein, mouse) SB - IM MH - Animals MH - Cell Line MH - *Gene Expression Regulation MH - Humans MH - Inflammation/genetics MH - Mice MH - Mice, Knockout MH - RNA-Binding Proteins/genetics/*physiology MH - Tristetraprolin/genetics/*physiology MH - Tumor Necrosis Factor-alpha/pharmacology/*physiology EDAT- 2012/09/22 06:00 MHDA- 2013/03/26 06:00 CRDT- 2012/09/22 06:00 PHST- 2012/08/20 00:00 [received] PHST- 2012/09/07 00:00 [accepted] PHST- 2012/09/22 06:00 [entrez] PHST- 2012/09/22 06:00 [pubmed] PHST- 2013/03/26 06:00 [medline] AID - S0006-291X(12)01773-1 [pii] AID - 10.1016/j.bbrc.2012.09.033 [doi] PST - ppublish SO - Biochem Biophys Res Commun. 2012 Nov 23;428(3):327-32. doi: 10.1016/j.bbrc.2012.09.033. Epub 2012 Sep 17.