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oxLDL downregulates the dendritic cell homing factors CCR7 and CCL21.

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 - Mediators Inflamm. (2012)

Bottom Line: 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).

View Article: PubMed Central - PubMed

Affiliation: Medizinische Klinik und Poliklinik I, Campus Grosshadern, Ludwig-Maximilians University, 81377 Munich, Germany. tsnickel@web.de

ABSTRACT

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.

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Protein expression of CD83 and CCR7 on DCs after stimulation with oxLDL. An increase of the expression of CD83 and a decrease of the expression of CCR7on DCs after stimulation with oxLDL (10 μg/mL) was observed. Positive cells were measured by flow cytometry and the percent (%) changes were plotted in the figure. *P < 0.05, (n = 8) versus unstimulated controls.
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fig3: Protein expression of CD83 and CCR7 on DCs after stimulation with oxLDL. An increase of the expression of CD83 and a decrease of the expression of CCR7on DCs after stimulation with oxLDL (10 μg/mL) was observed. Positive cells were measured by flow cytometry and the percent (%) changes were plotted in the figure. *P < 0.05, (n = 8) versus unstimulated controls.

Mentions: After stimulation with oxLDL, we found a reduction of the mRNA levels of CCR7 (DCs) by 30% using RT-PCR (n = 8; P < 0.05). This correlated with a reduction in protein expression by 46% (n = 8; 25.7 ± 1.06% versus control 47.6 ± 19.3% positive cells; P < 0.05; Figure 3). In contrast, protein expression of CD83 was significantly upregulated by 10 μg/mL oxLDL, as shown in Figure 3 (60%, 46.9 ± 11.3 versus control 29.3 ± 17.7% positive cells; P < 0.05; Figure 2) by 10 μg/mL oxLDL (Figure 3).


oxLDL downregulates the dendritic cell homing factors CCR7 and CCL21.

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 - Mediators Inflamm. (2012)

Protein expression of CD83 and CCR7 on DCs after stimulation with oxLDL. An increase of the expression of CD83 and a decrease of the expression of CCR7on DCs after stimulation with oxLDL (10 μg/mL) was observed. Positive cells were measured by flow cytometry and the percent (%) changes were plotted in the figure. *P < 0.05, (n = 8) versus unstimulated controls.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3350855&req=5

fig3: Protein expression of CD83 and CCR7 on DCs after stimulation with oxLDL. An increase of the expression of CD83 and a decrease of the expression of CCR7on DCs after stimulation with oxLDL (10 μg/mL) was observed. Positive cells were measured by flow cytometry and the percent (%) changes were plotted in the figure. *P < 0.05, (n = 8) versus unstimulated controls.
Mentions: After stimulation with oxLDL, we found a reduction of the mRNA levels of CCR7 (DCs) by 30% using RT-PCR (n = 8; P < 0.05). This correlated with a reduction in protein expression by 46% (n = 8; 25.7 ± 1.06% versus control 47.6 ± 19.3% positive cells; P < 0.05; Figure 3). In contrast, protein expression of CD83 was significantly upregulated by 10 μg/mL oxLDL, as shown in Figure 3 (60%, 46.9 ± 11.3 versus control 29.3 ± 17.7% positive cells; P < 0.05; Figure 2) by 10 μg/mL oxLDL (Figure 3).

Bottom Line: 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).

View Article: PubMed Central - PubMed

Affiliation: Medizinische Klinik und Poliklinik I, Campus Grosshadern, Ludwig-Maximilians University, 81377 Munich, Germany. tsnickel@web.de

ABSTRACT

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.

Show MeSH
Related in: MedlinePlus