PMID- 19955845 OWN - NLM STAT- MEDLINE DCOM- 20100318 LR - 20131121 IS - 1423-0313 (Electronic) IS - 0031-7012 (Linking) VI - 85 IP - 1 DP - 2010 TI - Curcumin attenuates glucose-induced monocyte chemoattractant protein-1 synthesis in aortic endothelial cells by modulating the nuclear factor-kappaB pathway. PG - 18-26 LID - 10.1159/000262325 [doi] AB - BACKGROUND/AIMS: High glucose (HG) induces monocyte chemoattractant protein-1 (MCP-1) synthesis in endothelial cells through nuclear factor kappaB (NFkappaB). We investigated whether curcumin, losartan and sodium salicylate (NaSal) attenuate HG-induced MCP-1 synthesis in rat aortic endothelial cells (RAECs) and explored the mechanism of action. METHODS: RAECs were stimulated with HG (25 mmol/l) for 24 h in the presence or absence of curcumin, losartan, NaSal or NFkappaB inhibitor, Bay 11-0782. The MCP-1 protein and mRNA levels were determined by enzyme-linked immunosorbent assay and real-time reverse transcriptase-polymerase chain reaction, respectively. Nuclear translocation of NFkappaB subunit p65 and NFkappaB DNA-binding activity was studied using confocal microscopy and electrophoretic mobility shift assay, respectively. RESULTS: A significant increase in the synthesis of MCP-1 protein and mRNA (2-fold) was observed in HG-primed RAECs compared to control glucose (5.5 mmol/l). Curcumin (30 micromol/l) significantly decreased HG-induced MCP-1 protein (74%) and mRNA (53%) synthesis. There was no inhibition of HG-induced MCP-1 protein secretion by losartan and NaSal. In HG-stimulated RAECs, curcumin attenuated the nuclear translocation of p65 and decreased the NFkappaB DNA-binding activity. CONCLUSION: Curcumin blocks HG-induced MCP-1 synthesis in RAECs partly via the NFkappaB pathway. CI - Copyright 2009 S. Karger AG, Basel. FAU - Panicker, Sumith Retnamma AU - Panicker SR AD - Division of Cellular and Molecular Cardiology, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Thiruvananthapuram, India. FAU - Kartha, Chandrasekharan Cheranellore AU - Kartha CC LA - eng PT - Comparative Study PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20091201 PL - Switzerland TA - Pharmacology JT - Pharmacology JID - 0152016 RN - 0 (Anti-Inflammatory Agents, Non-Steroidal) RN - 0 (Chemokine CCL2) RN - 0 (NF-kappa B) RN - 0 (RNA, Messenger) RN - IT942ZTH98 (Curcumin) RN - IY9XDZ35W2 (Glucose) RN - JMS50MPO89 (Losartan) RN - WIQ1H85SYP (Sodium Salicylate) SB - IM MH - Animals MH - Anti-Inflammatory Agents, Non-Steroidal/pharmacology MH - Aorta/cytology/drug effects/metabolism MH - Chemokine CCL2/biosynthesis/*drug effects MH - Curcumin/*pharmacology MH - Endothelium, Vascular/drug effects/metabolism MH - Enzyme-Linked Immunosorbent Assay MH - Glucose/administration & dosage/*pharmacology MH - Losartan/pharmacology MH - Male MH - NF-kappa B/*metabolism MH - RNA, Messenger/drug effects/metabolism MH - Rats MH - Rats, Sprague-Dawley MH - Reverse Transcriptase Polymerase Chain Reaction MH - Sodium Salicylate/pharmacology EDAT- 2009/12/04 06:00 MHDA- 2010/03/20 06:00 CRDT- 2009/12/04 06:00 PHST- 2009/07/14 00:00 [received] PHST- 2009/09/03 00:00 [accepted] PHST- 2009/12/04 06:00 [entrez] PHST- 2009/12/04 06:00 [pubmed] PHST- 2010/03/20 06:00 [medline] AID - 000262325 [pii] AID - 10.1159/000262325 [doi] PST - ppublish SO - Pharmacology. 2010;85(1):18-26. doi: 10.1159/000262325. Epub 2009 Dec 1.