oxLDL downregulates the dendritic cell homing factors CCR7 and CCL21

  • 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.

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Author:Thomas Nickel, Susanne Pfeiler, Claudia Summo, Reinhard Kopp, Georgios Meimarakis, Zeljka Sicic, Marius Lambert, Korbinian Johannes Lackermair, Robert David, Andrés Beiras FernándezGND, Ingo Kaczmarek, Michael Weis
URN:urn:nbn:de:hebis:30:3-245713
DOI:https://doi.org/10.1155/2012/320953
ISSN:1466-1861
ISSN:0962-9351
Pubmed Id:https://pubmed.ncbi.nlm.nih.gov/22619482
Parent Title (English):Mediators of inflammation
Publisher:Hindawi Publishing Corp.
Place of publication:Sylvania, Ohio
Document Type:Article
Language:English
Date of Publication (online):2012/05/31
Date of first Publication:2012/04/30
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2012/05/31
Volume:2012
Issue:Article ID 320953
Page Number:10
HeBIS-PPN:306534363
Institutes:Medizin / Medizin
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Sammlungen:Universitätspublikationen
Licence (German):License LogoCreative Commons - Namensnennung 3.0