| Article ID | Journal | Published Year | Pages | File Type |
|---|---|---|---|---|
| 5832728 | International Immunopharmacology | 2014 | 6 Pages |
â¢Dexamethasone reduces IL-8 secretion and decreases IL-8 mRNA stabilization in HPMECs.â¢Dexamethasone increases TTP expression in HPMEC.â¢TTP promotes IL-8 mRNA decay and negatively regulates IL-8 expression.
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 3â²-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.
Graphical abstractDownload full-size image
