Vol 11: Up-regulation of COX-2-PGE2 by endothelin-1 via MAPK-dependent NF-B pathway in mouse brain microvascular endothelial cells.Report as inadecuate



 Vol 11: Up-regulation of COX-2-PGE2 by endothelin-1 via MAPK-dependent NF-B pathway in mouse brain microvascular endothelial cells.


Vol 11: Up-regulation of COX-2-PGE2 by endothelin-1 via MAPK-dependent NF-B pathway in mouse brain microvascular endothelial cells. - Download this document for free, or read online. Document in PDF available to download.

Download or read this book online for free in PDF: Vol 11: Up-regulation of COX-2-PGE2 by endothelin-1 via MAPK-dependent NF-B pathway in mouse brain microvascular endothelial cells.
This article is from Cell Communication and Signaling : CCS, volume 11.AbstractBackground: Endothelin-1 ET-1 is a proinflammatory mediator and elevated in the regions of several brain injury and inflammatory diseases. The deleterious effects of ET-1 on endothelial cells may aggravate brain inflammation mediated through the regulation of cyclooxygenase-2 COX-2-prostaglandin E2 PGE2 system in various cell types. However, the signaling mechanisms underlying ET-1-induced COX-2 expression in brain microvascular endothelial cells remain unclear. Herein we investigated the effects of ET-1 in COX-2 regulation in mouse brain microvascular endothelial bEnd.3 cells. Results: The data obtained with Western blotting, RT-PCR, and immunofluorescent staining analyses showed that ET-1-induced COX-2 expression was mediated through an ETB-dependent transcriptional activation. Engagement of Gi- and Gq-protein-coupled ETB receptors by ET-1 led to phosphorylation of ERK1-2, p38 MAPK, and JNK1-2 and then activated transcription factor NF-κB. Moreover, the data of chromatin immunoprecipitation ChIP and promoter reporter assay demonstrated that the activated NF-κB was translocated into nucleus and bound to its corresponding binding sites in COX-2 promoter, thereby turning on COX-2 gene transcription. Finally, up-regulation of COX-2 by ET-1 promoted PGE2 release in these cells. Conclusions: These results suggested that in mouse bEnd.3 cells, activation of NF-κB by ETB-dependent MAPK cascades is essential for ET-1-induced up-regulation of COX-2-PGE2 system. Understanding the mechanisms of COX-2 expression and PGE2 release regulated by ET-1-ETB system on brain microvascular endothelial cells may provide rationally therapeutic interventions for brain injury or inflammatory diseases.



Author: Lin, Chih-Chung; Hsieh, Hsi-Lung; Shih, Ruey-Horng; Chi, Pei-Ling; Cheng, Shin-Ei; Yang, Chuen-Mao

Source: https://archive.org/







Related documents