Effect of caffeic acid on tumor necrosis factor-alpha-induced vascular inflammation in human umbilical vein endothelial cells.

Recruitment of specific leukocyte subpopulations at the site of inflammation requires a series of cell adhesion molecules (CAMs)-mediated interactions. The major CAMs, viz., intracellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and E-selectin are expressed on endothelium in response to various cytokines. Caffeic acid (CA), a natural phenolic compound from herbs and other sources, has been shown to prevent cardiovascular diseases. We investigated the effect of CA on the expression of CAMs by human umbilical vein endothelial cells (HUVECs) stimulated with tumor necrosis factor (TNF-alpha). Adhesion of monocytes to CA-treated HUVECs was evaluated by co-culture experiments using 2,7-bis(2-carboxyethyl)-5(6)-carboxyfluorescein acetoxymethylester (BCECF-AM) labeling of U937 cells. The expression of adhesion and chemoattractant molecules was evaluated by Western blot and reverse transcription-polymerase chain reaction (RT-PCR), respectively. CA significantly inhibited the TNF-alpha-induced increase in U937 monocyte adhesion to HUVECs as well as decreased the protein and mRNA expression levels of CAMs on HUVECs. CA also inhibited the mRNA expression of monocyte chemoattractant protein-1 (MCP-1) and interleukin-8 (IL-8). The involvement of nuclear factor (NF)-kappaB in the transcriptional control of CAMs protein was assessed by degradation of inhibitory (I)kappaB and nuclear translocation of NF-kappaB using Western blotting and immunofluorescence staining. CA attenuated TNF-alpha-induced IkappaB degradation and NF-kappaB translocation from cytosol to the nucleus. In conclusion, TNF-alpha-induced NF-kappaB-DNA complex formation was inhibited by CA. CA reduced TNF-alpha-induced endothelial adhesiveness to HUVECs by inhibiting transcription factor activation, and CAMs expression suggesting its potential role in atherosclerosis diseases.