title: Tristetraprolin is involved in the glucocorticoid-mediated interleukin 8 repression.
abstract: Glucocorticoids have been widely used in various inflammatory disorders, and the transcriptional repression of inflammatory mediators has been considered to be the main mechanism of action. However, a previous study showed that dexamethasone inhibited interleukin 8 (IL-8) expression by promoting IL-8 mRNA decay, which implies a posttranscriptional regulation. Nevertheless, by which mechanism dexamethasone destabilized IL-8 mRNA was unclear. Another study indicated that an RNA-binding protein, tristetraprolin (TTP), could be induced by dexamethasone. TTP can bind to AU-rich elements (ARE) in the 3'-untranslated region of target mRNAs and promotes mRNA degradation. So, we speculated that dexamethasone destabilized IL-8 mRNA by upregulating TTP expression. Here, we report that dexamethasone reduced IL-8 expression through destabilizing IL-8 mRNA in human pulmonary microvascular endothelial cells (HPMECs). Dexamethasone stimulation increased TTP mRNA and protein levels. TTP silencing led to mRNA stabilization and protein upregulation of IL-8. These results provide the evidence that the glucocorticoid, in HPMECs, inhibits IL-8 expression through TTP at the posttranscriptional level.
authors.affiliation: Department of Respiratory Medicine, Lianyungang First People's Hospital, Affiliated Hospital of Xuzhou Medical College, Clinical Medical School of Nanjing Medical University, Lianyungang 222002, China. Electronic address: shijiaxin919@126.com.
authors.forename: Jia-Xin
authors.initials: JX
authors.lastname: Shi
authors.affiliation: Department of Respiratory Medicine, Lianyungang First People's Hospital, Affiliated Hospital of Xuzhou Medical College, Clinical Medical School of Nanjing Medical University, Lianyungang 222002, China. Electronic address: ljssm1118@sina.com.
authors.forename: Jia-Shu
authors.initials: JS
authors.lastname: Li
authors.affiliation: Department of Respiratory Medicine, Lianyungang First People's Hospital, Affiliated Hospital of Xuzhou Medical College, Clinical Medical School of Nanjing Medical University, Lianyungang 222002, China.
authors.forename: Rong
authors.initials: R
authors.lastname: Hu
authors.affiliation: Department of Respiratory and Critical Care Medicine, Jinling Hospital, Nanjing University School of Medicine, Nanjing 210002, China. Electronic address: shiyi56@126.com.
authors.forename: Yi
authors.initials: Y
authors.lastname: Shi
authors.affiliation: Department of Respiratory and Critical Care Medicine, Jinling Hospital, Nanjing University School of Medicine, Nanjing 210002, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Su
authors.affiliation: Department of Respiratory Medicine, Lianyungang First People's Hospital, Affiliated Hospital of Xuzhou Medical College, Clinical Medical School of Nanjing Medical University, Lianyungang 222002, China.
authors.forename: Xiang-Jun
authors.initials: XJ
authors.lastname: Guo
authors.affiliation: Department of Respiratory Medicine, Lianyungang First People's Hospital, Affiliated Hospital of Xuzhou Medical College, Clinical Medical School of Nanjing Medical University, Lianyungang 222002, China.
authors.forename: Xiao-Mei
authors.initials: XM
authors.lastname: Li
mesh_terms: D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D003907:Dexamethasone / Q000494:pharmacology*; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D005938:Glucocorticoids / Q000494:pharmacology*; D006801:Humans; D016209:Interleukin-8 / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D051816:Tristetraprolin / Q000235:genetics / Q000378:metabolism*
chemical_list: C508606:CXCL8 protein, human; D005938:Glucocorticoids; D016209:Interleukin-8; D012333:RNA, Messenger; D051816:Tristetraprolin; D003907:Dexamethasone
keywords: AU-rich element; Glucocorticoid; Human pulmonary microvascular endothelial cells; Interleukin-8 (IL-8); Tristetraprolin (TTP)