| First Author | Burek M | Year | 2009 |
| Journal | Mol Cell Endocrinol | Volume | 298 |
| Issue | 1-2 | Pages | 19-24 |
| PubMed ID | 18996436 | Mgi Jnum | J:146978 |
| Mgi Id | MGI:3839049 | Doi | 10.1016/j.mce.2008.09.041 |
| Citation | Burek M, et al. (2009) Cloning and characterization of the murine claudin-5 promoter. Mol Cell Endocrinol 298(1-2):19-24 |
| abstractText | Claudin-5, an integral tight junction protein component, plays a critical role in permeability of the endothelial cell barrier. Recently, we have shown that claudin-5 protein is down-regulated by the proinflammatory cytokine TNF alpha and its levels restored by dexamethasone treatment. In order to investigate the regulation of claudin-5 at the transcriptional level, we have cloned the murine claudin-5 promoter. The claudin-5 promoter sequence (1131 bp) showed no consensus TATA-box. We identified putative transcription factor binding sites, including six full and two half sites degenerated glucocorticoid-response elements (GREs), two NFkappaB, three Sp1, one Sp2, one Ap2, as well as three E-boxes. Serially deleted promoter constructs showed high basal activity. TNF alpha significantly reduced the promoter activity and mRNA levels of claudin-5 in brain cEND and myocardial MyEND endothelial cells. Dexamethasone treatment led to a significant increase of the murine claudin-5 promoter activity and mRNA levels in cEND cells. However, no claudin-5 induction could be observed in MyEND cells in response to dexamethasone. Our studies suggest tissue-specific regulation of the claudin-5 gene via glucocorticoids and a high vulnerability of claudin-5 to TNF alpha. This could be an important mechanism in diseases accompanied by the release of proinflammatory cytokines, for example in patients with chronic heart failure or multiple sclerosis. |
