Quercetin attenuates Monocyte Chemoattractant Protein-1 gene expression in glucose primed aortic endothelial cells through NF-κB and AP-1

Panicker, Sumith Retnamma ; Sreenivas, Prethish ; Babu, Mani Sankar ; Karunagaran, Devarajan ; Kartha, Chandrasekharan Cheranellore (2010) Quercetin attenuates Monocyte Chemoattractant Protein-1 gene expression in glucose primed aortic endothelial cells through NF-κB and AP-1 Pharmacological Research, 62 (4). pp. 328-336. ISSN 1043-6618

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Official URL: http://linkinghub.elsevier.com/retrieve/pii/S10436...

Related URL: http://dx.doi.org/10.1016/j.phrs.2010.06.003

Abstract

Monocyte Chemoattractant Protein-1 (MCP-1) is involved in the diapedesis of blood monocytes into the arterial intima, an early critical event in atherogenesis. Modulating MCP-1 expression can be a key strategy to decrease the risk for atherosclerosis in diabetes. We hypothesized that quercetin, an anti-inflammatory molecule could modulate high glucose concentration (HG) induced MCP-1 expression in aortic endothelial cells in vitro because of its regulatory effects on Activator Protein-1 (AP-1) and Nuclear Factor-κB (NF-κB). Rat aortic endothelial cells (RAECs) were exposed to HG in the presence or absence of quercetin. Quercetin attenuated HG induced MCP-1 mRNA (42%) and protein synthesis (45%) when estimated using real-time reverse transcriptase-polymerase chain reaction and enzyme-linked immunosorbent assay respectively. Western blot analysis found quercetin to maintain cytosolic p65 protein levels to that seen in control. Quercetin was found to attenuate HG induced increased NF-κB and AP-1 DNA binding activity in electrophoretic mobility shift assay. Immunofluorescence studies revealed quercetin to prevent HG induced nuclear localization of p65 and c-jun. Quercetin was also found to decrease HG induced activation of NF-κB (71% ± 14%), AP-1 (69% ± 24%) and MCP-1 promoter (79% ± 25%) in EA.hy926 cells when analyzed using luciferase reporter assay. We conclude that quercetin attenuates MCP-1 expression in HG treated RAECs, probably by regulating both NF-κB and AP-1 pathways. The findings provide new insights into HG induced MCP-1 gene regulation in aortic endothelial cells and the potential of quercetin in abating the risk for atherosclerosis in diabetes.

Item Type:Article
Source:Copyright of this article belongs to Elsevier Science.
Keywords:Monocyte Chemoattractant Protein-1; Quercetin; Glucose; Endothelial Cells; NF-κB; AP-1
ID Code:18186
Deposited On:17 Nov 2010 13:01
Last Modified:21 Feb 2011 08:10

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