PMID- 20542118 OWN - NLM STAT- MEDLINE DCOM- 20101129 LR - 20150831 IS - 1096-1186 (Electronic) IS - 1043-6618 (Linking) VI - 62 IP - 4 DP - 2010 Oct TI - Quercetin attenuates Monocyte Chemoattractant Protein-1 gene expression in glucose primed aortic endothelial cells through NF-kappaB and AP-1. PG - 328-36 LID - 10.1016/j.phrs.2010.06.003 [doi] AB - 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-kappaB (NF-kappaB). 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-kappaB 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-kappaB (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-kappaB 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. CI - Copyright 2010 Elsevier Ltd. All rights reserved. FAU - Panicker, Sumith Retnamma AU - Panicker SR AD - Division of Cellular and Molecular Cardiology, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Kerala, India. FAU - Sreenivas, Prethish AU - Sreenivas P FAU - Babu, Mani Sankar AU - Babu MS FAU - Karunagaran, Devarajan AU - Karunagaran D FAU - Kartha, Chandrasekharan Cheranellore AU - Kartha CC LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20100611 PL - Netherlands TA - Pharmacol Res JT - Pharmacological research JID - 8907422 RN - 0 (Anti-Inflammatory Agents) RN - 0 (Chemokine CCL2) RN - 0 (NF-kappa B) RN - 0 (Proto-Oncogene Proteins c-jun) RN - 0 (Reactive Oxygen Species) RN - 0 (Transcription Factor AP-1) RN - 9IKM0I5T1E (Quercetin) RN - IY9XDZ35W2 (Glucose) SB - IM MH - Animals MH - Anti-Inflammatory Agents/*pharmacology MH - Aorta/cytology MH - Cells, Cultured MH - Chemokine CCL2/*genetics MH - Endothelial Cells/*drug effects/metabolism MH - Gene Expression Regulation/*drug effects MH - Glucose/metabolism MH - Male MH - NF-kappa B/*metabolism MH - Promoter Regions, Genetic/drug effects MH - Protein Transport/drug effects MH - Proto-Oncogene Proteins c-jun/metabolism MH - Quercetin/*pharmacology MH - Rats MH - Rats, Sprague-Dawley MH - Reactive Oxygen Species/metabolism MH - Transcription Factor AP-1/*metabolism EDAT- 2010/06/15 06:00 MHDA- 2010/12/14 06:00 CRDT- 2010/06/15 06:00 PHST- 2010/01/22 00:00 [received] PHST- 2010/06/07 00:00 [revised] PHST- 2010/06/07 00:00 [accepted] PHST- 2010/06/15 06:00 [entrez] PHST- 2010/06/15 06:00 [pubmed] PHST- 2010/12/14 06:00 [medline] AID - S1043-6618(10)00126-X [pii] AID - 10.1016/j.phrs.2010.06.003 [doi] PST - ppublish SO - Pharmacol Res. 2010 Oct;62(4):328-36. doi: 10.1016/j.phrs.2010.06.003. Epub 2010 Jun 11.