Effect of Caffeic Acid on Tumor Necrosis Factor-Alpha-Induced Vascular Inflammation in Human Umbilical Vein Endothelial Cells

Abstract

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-a a). Adhesion of monocytes to CAtreated 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-a a-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)-k kB in the transcriptional control of CAMs protein was assessed by degradation of inhibitory (I)k kB and nuclear translocation of NF-k kB using Western blotting and immunofluorescence staining. CA attenuated TNF-a ainduced Ik kB degradation and NF-k kB translocation from cytosol to the nucleus. In conclusion, TNF-a a-induced NF-k kB-DNA complex formation was inhibited by CA. CA reduced TNF-a a-induced endothelial adhesiveness to HUVECs by inhibiting transcription factor activation, and CAMs expression suggesting its potential role in atherosclerosis diseases.

Caffeic Acid Reduces Cutaneous Tumor Necrosis Factor Alpha (TNF-α), IL-6 and IL-1β Levels and Ameliorates Skin Edema in Acute and Chronic Model of Cutaneous Inflammation in Mice

“…19) Our findings also demonstrated that CA reduced TNF-α-induced NF-κB activation in human keratinocytes. The findings suggested that CA might effectively modulate the transcriptional activity of NF-κB in cutaneous inflammatory responses, which is critical for the transcriptional regulation of many pro-inflammatory cytokines.…”

“…Since CA was demonstrated to have an ability to reduce TNF-α-induced vascular inflammation by targeting pathways that result in the activation of the nuclear transcription factor NF-κB, 19) we further investigated whether CA treatment decreased the NF-κB activity in human keratinocytes. Keratinocyte cells were transiently transfected with pNF-κB-Luc reporter plasmid, stimulated with 10 ng/mL TNF-α in the presence or absence of CA, and then measured the luciferase acitivty, which served as an indicator of NF-κB activation.…”

“…Our finding is consistent with the findings in human umbilical vein endothelial cells and HaCaT cells. 19,20) Effect of CA on Chronic Inflammation Induced by Repeated Application of TPA As a second in vivo evaluation of the anti-inflammatory activity of CA, CA was administered in a chronic skin inflammation model induced by multiple topical applications of TPA to mouse ears. A inflammatory response characterized by increases in ear weight, inflammatory cell infiltration and epidermal hyperplasia is persistent in this model.…”

“…Many studies have shown that this compound possesses anti-inflammatory activity. [9][10][11] The study of Chao et al revealed that CA could provide anti-inflammatory protection by down-regulated TNF-α, IL-6, and IL-1β mRNA and protein expression in cardiac tissue of diabetic mice. 12) Khan et al observed that CA attenuates 12-O-tetradecanoyl-phorbol-13-acetate (TPA)-induced tumor promotional triggers by inhibition of oxidative stress and pro-inflammatory cytokine production.…”

Chlorophyll-Related Compounds Inhibit Cell Adhesion and Inflammation in Human Aortic Cells

“…15 Several types of natural antioxidants, including flavonoids and polyphenolic compounds, inhibit adhesion molecule expression, and the adhesion of monocytes to endothelial cells, and are believed to suppress inflammation, transformation, proliferation, survival, invasion, and angiogenesis. 16,17 Chlorophylls (Chls), the most abundant green pigments found in plants, are important in photosynthesis. Chls are constituents of the diet, especially from green vegetables and fruits.…”