Curcumin attenuates glucose-induced monocyte chemoattractant protein-1 synthesis in aortic endothelial cells by modulating the nuclear factor-kappaB pathway.
OBJECTIVE
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.


CONCLUSIONS
Curcumin blocks HG-induced MCP-1 synthesis in RAECs partly via the NFkappaB pathway.
Panicker
Sumith Retnamma
SR
Division of Cellular and Molecular Cardiology, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Thiruvananthapuram, India.
Kartha
Chandrasekharan Cheranellore
CC
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D001011:Aorta / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D018932:Chemokine CCL2 / Q000096:biosynthesis / Q000187:drug effects*; D003474:Curcumin / Q000494:pharmacology*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005947:Glucose / Q000008:administration & dosage / Q000494:pharmacology*; D019808:Losartan / Q000494:pharmacology; D008297:Male; D016328:NF-kappa B / Q000378:metabolism*; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012980:Sodium Salicylate / Q000494:pharmacology
D000894:Anti-Inflammatory Agents, Non-Steroidal; D018932:Chemokine CCL2; D016328:NF-kappa B; D012333:RNA, Messenger; D003474:Curcumin; D005947:Glucose; D019808:Losartan; D012980:Sodium Salicylate