Curcumin (Diferuloylmethane) inhibition of tumor necrosis factor (TNF)-mediated adhesion of monocytes to endothelial cells by suppression of cell surface expression of adhesion molecules and of nuclear factor-kappaB activation.
Recruitment of leukocytes by endothelial cells and their subsequent migration from the vasculature into the tissue play major roles in inflammation. In the present study, we investigated the effect of curcumin, an antiinflammatory agent, on the adhesion of monocytes to human umbilical vein endothelial cells (EC). Treatment of EC with tumor necrosis factor (TNF) for 6 hr augmented the adhesion of monocytes to EC, and this adhesion was due to increased expression of intracellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and endothelial leukocyte adhesion molecule-1 (ELAM-1). Pretreatment of EC for 1 hr with curcumin completely blocked their adhesion to monocytes, as well as the cell surface expression of ICAM-1, VCAM-1, and ELAM-1 in EC. Although curcumin inhibited adhesion even when administered 1 hr after TNF treatment, maximum inhibition occurred when added either 1 hr before or at the same time as TNF. As the induction of various adhesion molecules by TNF requires activation of the transcription factor NF-kappaB, the effect of curcumin on the activation of this factor in the EC was also investigated. A 30-min treatment with TNF activated NF-kappaB; the activation was inhibited in a concentration-dependent manner by pretreatment with curcumin, indicating that NF-kappaB inhibition may play a role in the suppression of expression of adhesion molecules in EC. Our results demonstrate that the antiinflammatory properties of curcumin may be attributable, in part, to inhibition of leukocyte recruitment.
Kumar
A
A
Department of Molecular Oncology, University of Texas M. D. Anderson Cancer Center, Houston 77030, USA.
Dhawan
S
S
Hardegen
N J
NJ
Aggarwal
B B
BB
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D000906:Antibodies / Q000276:immunology; D002448:Cell Adhesion / Q000187:drug effects; D015815:Cell Adhesion Molecules / Q000032:analysis*; D002462:Cell Membrane / Q000187:drug effects; D003474:Curcumin / Q000494:pharmacology*; D003864:Depression, Chemical; D019040:E-Selectin / Q000276:immunology; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects*; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000276:immunology; D009000:Monocytes / Q000166:cytology / Q000187:drug effects*; D016328:NF-kappa B / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*; D019010:Vascular Cell Adhesion Molecule-1 / Q000276:immunology
D000894:Anti-Inflammatory Agents, Non-Steroidal; D000906:Antibodies; D015815:Cell Adhesion Molecules; D019040:E-Selectin; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D003474:Curcumin