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PMID: 22619482 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

oxLDL downregulates the dendritic cell homing factors CCR7 and CCL21.

Mediators of inflammation ·Vol. 2012 ·2012-00-00 ·Pages 320953

Nickel T, Pfeiler S, Summo C, Kopp R, Meimarakis G, Sicic Z, Lambert M, Lackermair K, David R, Beiras-Fernandez A, Kaczmarek I, Weis M

Abstract

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. 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). 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.

MeSH Terms
Atherosclerosis/pathology Carotid Arteries/pathology Carotid Stenosis/pathology Cell Movement Chemokine CCL19/metabolism Chemokine CCL21/metabolism Dendritic Cells/cytology Disease Progression Down-Regulation Endothelial Cells/cytology,metabolism Humans Ligands Lipoproteins, LDL/metabolism Microcirculation Microscopy, Fluorescence/methods Monocytes/cytology Receptors, CCR7/metabolism
Chemicals
CCL19 protein, human CCL21 protein, human CCR7 protein, human Chemokine CCL19 Chemokine CCL21 Ligands Lipoproteins, LDL Receptors, CCR7 oxidized low density lipoprotein
Authors & Affiliations
12 authors, click to expand affiliations / ORCID
Nickel Thomas
Medizinische Klinik und Poliklinik I, Campus Grosshadern, Ludwig-Maximilians University, 81377 Munich, Germany. [email protected]
Pfeiler Susanne
Summo Claudia
Kopp Reinhard
Meimarakis Georgios
Sicic Zeljka
Lambert Marius
Lackermair Korbinian
David Robert
Beiras-Fernandez Andres
Kaczmarek Ingo
Weis Michael
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Article Info
Journal
Mediators of inflammation
Abbr.
Mediators Inflamm
ISSN
1466-1861
DOI
10.1155/2012/320953
Email
[email protected]
Published
2012-00-00
Epub
2012-00-30
Pages
320953
Language
English
Region
United States
NLM ID
9209001
PMCID
PMC3350855
Subset
IM
External Links
PubMed source DOI: 10.1155/2012/320953 PMC Full Text View journal details
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