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| Content Provider | Springer Nature : BioMed Central |
|---|---|
| Author | Lin, Chih-Chung Hsieh, Hsi-Lung Shih, Ruey-Horng Chi, Pei-Ling Cheng, Shin-Ei Yang, Chuen-Mao |
| Abstract | Background 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. |
| Related Links | https://biosignaling.biomedcentral.com/counter/pdf/10.1186/1478-811X-11-8.pdf |
| Ending Page | 14 |
| Page Count | 14 |
| Starting Page | 1 |
| File Format | HTM / HTML |
| DOI | 10.1186/1478-811X-11-8 |
| Journal | Cell Communication and Signaling |
| Issue Number | 1 |
| Volume Number | 11 |
| Language | English |
| Publisher | BioMed Central |
| Publisher Date | 2013-01-23 |
| Access Restriction | Open |
| Subject Keyword | Cell Biology Protein-Ligand Interactions Receptors Cytokines and Growth Factors Endothelin-1 COX-2 MAPK NF-κB Brain microvascular endothelial cells |
| Content Type | Text |
| Resource Type | Article |
| Subject | Biochemistry Cell Biology Molecular Biology |
| Journal Impact Factor | 8.2/2023 |
| 5-Year Journal Impact Factor | 8/2023 |
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