title: Curcumin attenuates glucose-induced monocyte chemoattractant protein-1 synthesis in aortic endothelial cells by modulating the nuclear factor-kappaB pathway.
abstract: 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.
authors: Division of Cellular and Molecular Cardiology, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Thiruvananthapuram, India.
authors: Sumith Retnamma
authors: SR
authors: Panicker
authors: Chandrasekharan Cheranellore
authors: CC
authors: Kartha
mesh_terms: 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
chemical_list: 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