Curcumin inhibits phorbol myristate acetate (PMA)-induced MCP-1 expression by inhibiting ERK and NF-κB transcriptional activity

Monocyte chemoattractant protein-1 (MCP-1) is a potent mediator of macrophage migration and therefore, plays an essential role in early events of inflammation. In the present study, we show the protein kinase C activator, phorbol myristate acetate (PMA), potently induced mRNA expression and secretion of the C-C chemokine MCP-1 in U937 cells. We found that curcumin, a natural biologically active compound extracted from rhizomes of Curcuma species, significantly inhibited the PMA-induced increase in MCP-1 expression and secretion. These effects of curcumin are dose dependent and correlate with the suppression of MCP-1 mRNA expression levels. Curcumin inhibited PMA-mediated activation of extracellular signal-regulated kinase (ERK) and NF-κB transcriptional activity. Therefore, one possible anti-inflammatory mechanism of curcumin may be to inhibit the secretions of inflammatory MCP-1 chemokine.