oxLDL Downregulates the Dendritic Cell Homing Factors CCR7 and CCL21

Introduction. Dendritic cells (DCs) and oxLDL play an important role in the atherosclerotic process with DCs accumulating in the plaques during plaque progression. Our aim was to investigate the role of oxLDL in the modulation of the DC homing-receptor CCR7 and endothelial-ligand CCL21. Methods and...

Full description

Saved in:
Bibliographic Details
Main Authors: Thomas Nickel, Susanne Pfeiler, Claudia Summo, Reinhard Kopp, Georgios Meimarakis, Zeljka Sicic, Marius Lambert, Korbinian Lackermair, Robert David, Andres Beiras-Fernandez, Ingo Kaczmarek, Michael Weis
Format: Article
Language:English
Published: Wiley 2012-01-01
Series:Mediators of Inflammation
Online Access:http://dx.doi.org/10.1155/2012/320953
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1850171635993149440
author Thomas Nickel
Susanne Pfeiler
Claudia Summo
Reinhard Kopp
Georgios Meimarakis
Zeljka Sicic
Marius Lambert
Korbinian Lackermair
Robert David
Andres Beiras-Fernandez
Ingo Kaczmarek
Michael Weis
author_facet Thomas Nickel
Susanne Pfeiler
Claudia Summo
Reinhard Kopp
Georgios Meimarakis
Zeljka Sicic
Marius Lambert
Korbinian Lackermair
Robert David
Andres Beiras-Fernandez
Ingo Kaczmarek
Michael Weis
author_sort Thomas Nickel
collection DOAJ
description Introduction. Dendritic cells (DCs) and oxLDL play an important role in the atherosclerotic process with DCs accumulating in the plaques during plaque progression. Our aim was to investigate the role of oxLDL in the modulation of the DC homing-receptor CCR7 and endothelial-ligand CCL21. Methods and Results. The expression of the DC homing-receptor CCR7 and its endothelial-ligand CCL21 was examined on atherosclerotic carotic plaques of 47 patients via qRT-PCR and immunofluorescence. In vitro, we studied the expression of CCR7 on DCs and CCL21 on human microvascular endothelial cells (HMECs) in response to oxLDL. CCL21- and CCR7-mRNA levels were significantly downregulated in atherosclerotic plaques versus non-atherosclerotic controls [90% for CCL21 and 81% for CCR7 (𝑃<0.01)]. In vitro, oxLDL reduced CCR7 mRNA levels on DCs by 30% and protein levels by 46%. Furthermore, mRNA expression of CCL21 was significantly reduced by 50% (𝑃<0.05) and protein expression by 24% in HMECs by oxLDL (𝑃<0.05). Conclusions. The accumulation of DCs in atherosclerotic plaques appears to be related to a downregulation of chemokines and their ligands, which are known to regulate DC migration. oxLDL induces an in vitro downregulation of CCR7 and CCL21, which may play a role in the reduction of DC migration from the plaques.
format Article
id doaj-art-9a6213b294fd4b368667897111153bf6
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-9a6213b294fd4b368667897111153bf62025-08-20T02:20:15ZengWileyMediators of Inflammation0962-93511466-18612012-01-01201210.1155/2012/320953320953oxLDL Downregulates the Dendritic Cell Homing Factors CCR7 and CCL21Thomas Nickel0Susanne Pfeiler1Claudia Summo2Reinhard Kopp3Georgios Meimarakis4Zeljka Sicic5Marius Lambert6Korbinian Lackermair7Robert David8Andres Beiras-Fernandez9Ingo Kaczmarek10Michael Weis11Medizinische Klinik und Poliklinik I, Campus Grosshadern, Ludwig-Maximilians University, 81377 Munich, GermanyInstitute of Clinical Chemistry, Campus Grosshadern, Ludwig-Maximilians University, 81377 Munich, GermanyMedizinische Klinik und Poliklinik I, Campus Grosshadern, Ludwig-Maximilians University, 81377 Munich, GermanyDepartment of Surgery, Campus Grosshadern, Ludwig-Maximilians University, 81377 Munich, GermanyDepartment of Surgery, Campus Grosshadern, Ludwig-Maximilians University, 81377 Munich, GermanyMedizinische Klinik und Poliklinik I, Campus Grosshadern, Ludwig-Maximilians University, 81377 Munich, GermanyMedizinische Klinik und Poliklinik I, Campus Grosshadern, Ludwig-Maximilians University, 81377 Munich, GermanyMedizinische Klinik und Poliklinik I, Campus Grosshadern, Ludwig-Maximilians University, 81377 Munich, GermanyMedizinische Klinik und Poliklinik I, Campus Grosshadern, Ludwig-Maximilians University, 81377 Munich, GermanyDepartment of Cardiothoracic Surgery, J. W. Goethe University, 61590 Frankfurt, GermanyDepartment of Cardiac Surgery, Campus Grosshadern, Ludwig-Maximilians University, 81377 Munich, GermanyMedizinische Klinik und Poliklinik I, Campus Grosshadern, Ludwig-Maximilians University, 81377 Munich, GermanyIntroduction. Dendritic cells (DCs) and oxLDL play an important role in the atherosclerotic process with DCs accumulating in the plaques during plaque progression. Our aim was to investigate the role of oxLDL in the modulation of the DC homing-receptor CCR7 and endothelial-ligand CCL21. Methods and Results. The expression of the DC homing-receptor CCR7 and its endothelial-ligand CCL21 was examined on atherosclerotic carotic plaques of 47 patients via qRT-PCR and immunofluorescence. In vitro, we studied the expression of CCR7 on DCs and CCL21 on human microvascular endothelial cells (HMECs) in response to oxLDL. CCL21- and CCR7-mRNA levels were significantly downregulated in atherosclerotic plaques versus non-atherosclerotic controls [90% for CCL21 and 81% for CCR7 (𝑃<0.01)]. In vitro, oxLDL reduced CCR7 mRNA levels on DCs by 30% and protein levels by 46%. Furthermore, mRNA expression of CCL21 was significantly reduced by 50% (𝑃<0.05) and protein expression by 24% in HMECs by oxLDL (𝑃<0.05). Conclusions. The accumulation of DCs in atherosclerotic plaques appears to be related to a downregulation of chemokines and their ligands, which are known to regulate DC migration. oxLDL induces an in vitro downregulation of CCR7 and CCL21, which may play a role in the reduction of DC migration from the plaques.http://dx.doi.org/10.1155/2012/320953
spellingShingle Thomas Nickel
Susanne Pfeiler
Claudia Summo
Reinhard Kopp
Georgios Meimarakis
Zeljka Sicic
Marius Lambert
Korbinian Lackermair
Robert David
Andres Beiras-Fernandez
Ingo Kaczmarek
Michael Weis
oxLDL Downregulates the Dendritic Cell Homing Factors CCR7 and CCL21
Mediators of Inflammation
title oxLDL Downregulates the Dendritic Cell Homing Factors CCR7 and CCL21
title_full oxLDL Downregulates the Dendritic Cell Homing Factors CCR7 and CCL21
title_fullStr oxLDL Downregulates the Dendritic Cell Homing Factors CCR7 and CCL21
title_full_unstemmed oxLDL Downregulates the Dendritic Cell Homing Factors CCR7 and CCL21
title_short oxLDL Downregulates the Dendritic Cell Homing Factors CCR7 and CCL21
title_sort oxldl downregulates the dendritic cell homing factors ccr7 and ccl21
url http://dx.doi.org/10.1155/2012/320953
work_keys_str_mv AT thomasnickel oxldldownregulatesthedendriticcellhomingfactorsccr7andccl21
AT susannepfeiler oxldldownregulatesthedendriticcellhomingfactorsccr7andccl21
AT claudiasummo oxldldownregulatesthedendriticcellhomingfactorsccr7andccl21
AT reinhardkopp oxldldownregulatesthedendriticcellhomingfactorsccr7andccl21
AT georgiosmeimarakis oxldldownregulatesthedendriticcellhomingfactorsccr7andccl21
AT zeljkasicic oxldldownregulatesthedendriticcellhomingfactorsccr7andccl21
AT mariuslambert oxldldownregulatesthedendriticcellhomingfactorsccr7andccl21
AT korbinianlackermair oxldldownregulatesthedendriticcellhomingfactorsccr7andccl21
AT robertdavid oxldldownregulatesthedendriticcellhomingfactorsccr7andccl21
AT andresbeirasfernandez oxldldownregulatesthedendriticcellhomingfactorsccr7andccl21
AT ingokaczmarek oxldldownregulatesthedendriticcellhomingfactorsccr7andccl21
AT michaelweis oxldldownregulatesthedendriticcellhomingfactorsccr7andccl21