Anti-Inflammatory Properties of Sirtuin 6 in Human Umbilical Vein Endothelial Cells
A prominent feature of inflammatory diseases is endothelial dysfunction. Factors associated with endothelial dysfunction include proinflammatory cytokines, adhesion molecules, and matrix degrading enzymes. At the transcriptional level, they are regulated by the histone deacetylase sirtuin (SIRT) 1 v...
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| Format: | Article |
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Wiley
2012-01-01
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| Series: | Mediators of Inflammation |
| Online Access: | http://dx.doi.org/10.1155/2012/597514 |
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| author | Martha Lappas |
| author_facet | Martha Lappas |
| author_sort | Martha Lappas |
| collection | DOAJ |
| description | A prominent feature of inflammatory diseases is endothelial dysfunction. Factors associated with endothelial dysfunction include proinflammatory cytokines, adhesion molecules, and matrix degrading enzymes. At the transcriptional level, they are regulated by the histone deacetylase sirtuin (SIRT) 1 via its actions on the proinflammatory transcription factor nuclear factor-κB (NF-κB). The role of SIRT6, also a histone deacetylase, in regulating inflammation in endothelial cells is not known. The aim of this study was to determine the effect of SIRT6 knockdown on inflammatory markers in human umbilical vein endothelial cells (HUVECs) in the presence of lipopolysaccharide (LPS). LPS decreased expression of SIRT6 in HUVECs. Knockdown of SIRT6 increased the expression of proinflammatory cytokines (IL-1β, IL-6, IL-8), COX-prostaglandin system, ECM remodelling enzymes (MMP-2, MMP-9 and PAI-1), the adhesion molecule ICAM-1, and proangiogenic growth factors VEGF and FGF-2; cell migration; cell adhesion to leukocytes. Loss of SIRT6 increased the expression of NF-κB, whereas overexpression of SIRT6 was associated with decreased NF-κB transcriptional activity. Taken together, these results demonstrate that the loss of SIRT6 in endothelial cells is associated with upregulation of genes involved in inflammation, vascular remodelling, and angiogenesis. SIRT6 may be a potential pharmacological target for inflammatory vascular diseases. |
| format | Article |
| id | doaj-art-23e75273d3e24b169fe46711d4853fa0 |
| institution | OA Journals |
| issn | 0962-9351 1466-1861 |
| language | English |
| publishDate | 2012-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Mediators of Inflammation |
| spelling | doaj-art-23e75273d3e24b169fe46711d4853fa02025-08-20T02:04:13ZengWileyMediators of Inflammation0962-93511466-18612012-01-01201210.1155/2012/597514597514Anti-Inflammatory Properties of Sirtuin 6 in Human Umbilical Vein Endothelial CellsMartha Lappas0Department of Obstetrics and Gynaecology, University of Melbourne, Heidelberg, VIC 3084, AustraliaA prominent feature of inflammatory diseases is endothelial dysfunction. Factors associated with endothelial dysfunction include proinflammatory cytokines, adhesion molecules, and matrix degrading enzymes. At the transcriptional level, they are regulated by the histone deacetylase sirtuin (SIRT) 1 via its actions on the proinflammatory transcription factor nuclear factor-κB (NF-κB). The role of SIRT6, also a histone deacetylase, in regulating inflammation in endothelial cells is not known. The aim of this study was to determine the effect of SIRT6 knockdown on inflammatory markers in human umbilical vein endothelial cells (HUVECs) in the presence of lipopolysaccharide (LPS). LPS decreased expression of SIRT6 in HUVECs. Knockdown of SIRT6 increased the expression of proinflammatory cytokines (IL-1β, IL-6, IL-8), COX-prostaglandin system, ECM remodelling enzymes (MMP-2, MMP-9 and PAI-1), the adhesion molecule ICAM-1, and proangiogenic growth factors VEGF and FGF-2; cell migration; cell adhesion to leukocytes. Loss of SIRT6 increased the expression of NF-κB, whereas overexpression of SIRT6 was associated with decreased NF-κB transcriptional activity. Taken together, these results demonstrate that the loss of SIRT6 in endothelial cells is associated with upregulation of genes involved in inflammation, vascular remodelling, and angiogenesis. SIRT6 may be a potential pharmacological target for inflammatory vascular diseases.http://dx.doi.org/10.1155/2012/597514 |
| spellingShingle | Martha Lappas Anti-Inflammatory Properties of Sirtuin 6 in Human Umbilical Vein Endothelial Cells Mediators of Inflammation |
| title | Anti-Inflammatory Properties of Sirtuin 6 in Human Umbilical Vein Endothelial Cells |
| title_full | Anti-Inflammatory Properties of Sirtuin 6 in Human Umbilical Vein Endothelial Cells |
| title_fullStr | Anti-Inflammatory Properties of Sirtuin 6 in Human Umbilical Vein Endothelial Cells |
| title_full_unstemmed | Anti-Inflammatory Properties of Sirtuin 6 in Human Umbilical Vein Endothelial Cells |
| title_short | Anti-Inflammatory Properties of Sirtuin 6 in Human Umbilical Vein Endothelial Cells |
| title_sort | anti inflammatory properties of sirtuin 6 in human umbilical vein endothelial cells |
| url | http://dx.doi.org/10.1155/2012/597514 |
| work_keys_str_mv | AT marthalappas antiinflammatorypropertiesofsirtuin6inhumanumbilicalveinendothelialcells |