PMID- 22619482 OWN - NLM STAT- MEDLINE DCOM- 20120920 LR - 20211021 IS - 1466-1861 (Electronic) IS - 0962-9351 (Print) IS - 0962-9351 (Linking) VI - 2012 DP - 2012 TI - oxLDL downregulates the dendritic cell homing factors CCR7 and CCL21. PG - 320953 LID - 10.1155/2012/320953 [doi] LID - 320953 AB - 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. FAU - Nickel, Thomas AU - Nickel T AD - Medizinische Klinik und Poliklinik I, Campus Grosshadern, Ludwig-Maximilians University, 81377 Munich, Germany. tsnickel@web.de FAU - Pfeiler, Susanne AU - Pfeiler S FAU - Summo, Claudia AU - Summo C FAU - Kopp, Reinhard AU - Kopp R FAU - Meimarakis, Georgios AU - Meimarakis G FAU - Sicic, Zeljka AU - Sicic Z FAU - Lambert, Marius AU - Lambert M FAU - Lackermair, Korbinian AU - Lackermair K FAU - David, Robert AU - David R FAU - Beiras-Fernandez, Andres AU - Beiras-Fernandez A FAU - Kaczmarek, Ingo AU - Kaczmarek I FAU - Weis, Michael AU - Weis M LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20120430 PL - United States TA - Mediators Inflamm JT - Mediators of inflammation JID - 9209001 RN - 0 (CCL19 protein, human) RN - 0 (CCL21 protein, human) RN - 0 (CCR7 protein, human) RN - 0 (Chemokine CCL19) RN - 0 (Chemokine CCL21) RN - 0 (Ligands) RN - 0 (Lipoproteins, LDL) RN - 0 (Receptors, CCR7) RN - 0 (oxidized low density lipoprotein) SB - IM MH - Atherosclerosis/pathology MH - Carotid Arteries/pathology MH - Carotid Stenosis/pathology MH - Cell Movement MH - Chemokine CCL19/metabolism MH - Chemokine CCL21/*metabolism MH - Dendritic Cells/*cytology MH - Disease Progression MH - *Down-Regulation MH - Endothelial Cells/cytology/metabolism MH - Humans MH - Ligands MH - Lipoproteins, LDL/*metabolism MH - Microcirculation MH - Microscopy, Fluorescence/methods MH - Monocytes/cytology MH - Receptors, CCR7/*metabolism PMC - PMC3350855 EDAT- 2012/05/24 06:00 MHDA- 2012/09/21 06:00 PMCR- 2012/04/30 CRDT- 2012/05/24 06:00 PHST- 2011/08/28 00:00 [received] PHST- 2012/02/14 00:00 [accepted] PHST- 2012/05/24 06:00 [entrez] PHST- 2012/05/24 06:00 [pubmed] PHST- 2012/09/21 06:00 [medline] PHST- 2012/04/30 00:00 [pmc-release] AID - 10.1155/2012/320953 [doi] PST - ppublish SO - Mediators Inflamm. 2012;2012:320953. doi: 10.1155/2012/320953. Epub 2012 Apr 30.