Curcumin, the active constituent of turmeric, inhibits amyloid peptide-induced cytochemokine gene expression and CCR5-mediated chemotaxis of THP-1 monocytes by modulating early growth response-1 transcription factor

J Neurochem. 2004 Dec;91(5):1199-210. doi: 10.1111/j.1471-4159.2004.02800.x.


Epidemiological studies show reduced risk of Alzheimer's disease (AD) among patients using non-steroidal inflammatory drugs (NSAID) indicating the role of inflammation in AD. Studies have shown a chronic CNS inflammatory response associated with increased accumulation of amyloid peptide and activated microglia in AD. Our previous studies showed that interaction of Abeta1-40 or fibrilar Abeta1-42 caused activation of nuclear transcription factor, early growth response-1 (Egr-1), which resulted in increased expression of cytokines (TNF-alpha and IL-1beta) and chemokines (MIP-1beta, MCP-1 and IL-8) in monocytes. We determined whether curcumin, a natural product known to have anti-inflammatory properties, suppressed Egr-1 activation and concomitant expression of cytochemokines. We show that curcumin (12.5-25 microm) suppresses the activation of Egr-1 DNA-binding activity in THP-1 monocytic cells. Curcumin abrogated Abeta1-40-induced expression of cytokines (TNF-alpha and IL-1beta) and chemokines (MIP-1beta, MCP-1 and IL-8) in both peripheral blood monocytes and THP-1 cells. We found that curcumin inhibited Abeta1-40-induced MAP kinase activation and the phosphorylation of ERK-1/2 and its downstream target Elk-1. We observed that curcumin inhibited Abeta1-40-induced expression of CCR5 but not of CCR2b in THP-1 cells. This involved abrogation of Egr-1 DNA binding in the promoter of CCR5 by curcumin as determined by: (i) electrophoretic mobility shift assay, (ii) transfection studies with truncated CCR5 gene promoter constructs, and (iii) chromatin immunoprecipitation analysis. Finally, curcumin inhibited chemotaxis of THP-1 monocytes in response to chemoattractant. The inhibition of Egr-1 by curcumin may represent a potential therapeutic approach to ameliorate the inflammation and progression of AD.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amyloid beta-Peptides / pharmacology*
  • Blotting, Western / methods
  • Cell Line
  • Cell Survival / drug effects
  • Chemotaxis / drug effects*
  • Chromatin / metabolism
  • Curcuma / chemistry*
  • Curcumin / pharmacology*
  • Cytokines / genetics
  • Cytokines / metabolism*
  • Cytokines / pharmacology
  • DNA-Binding Proteins / metabolism
  • Dose-Response Relationship, Drug
  • Drug Interactions
  • Early Growth Response Protein 1
  • Electrophoretic Mobility Shift Assay / methods
  • Enzyme Inhibitors / pharmacology
  • Gene Expression / drug effects*
  • Humans
  • Immediate-Early Proteins / metabolism
  • Immunoprecipitation / methods
  • Monocytes / drug effects
  • Monocytes / physiology
  • Oligodeoxyribonucleotides, Antisense / pharmacology
  • Peptide Fragments / pharmacology*
  • RNA, Messenger / metabolism
  • Receptors, CCR5 / genetics
  • Receptors, CCR5 / metabolism*
  • Transcription Factors / metabolism
  • Transfection / methods


  • Amyloid beta-Peptides
  • Chromatin
  • Cytokines
  • DNA-Binding Proteins
  • EGR1 protein, human
  • Early Growth Response Protein 1
  • Enzyme Inhibitors
  • Immediate-Early Proteins
  • Oligodeoxyribonucleotides, Antisense
  • Peptide Fragments
  • RNA, Messenger
  • Receptors, CCR5
  • Transcription Factors
  • amyloid beta-protein (1-40)
  • amyloid beta-protein (1-42)
  • Curcumin