TY - JOUR
T1 - Inhibitory effects of lycopene on HMGB1-mediated pro-inflammatory responses in both cellular and animal models
AU - Lee, Wonhwa
AU - Ku, Sae Kwang
AU - Bae, Jae Woan
AU - Bae, Jong Sup
PY - 2012/6
Y1 - 2012/6
N2 - High mobility group box 1 (HMGB1) mediates proinflammatory responses in inflammatory diseases. Lycopene found in tomatoes and tomato products has anti-oxidant, anti-cancer and antiinflammatory effects. The potential anti-inflammatory roles of lycopene in HMGB1-mediated proinflammatory responses in both primary human umbilical vein endothelial cells (HUVECs) and animal were investigated. The anti-inflammatory effects of lycopene were determined including permeability, monocyte adhesion and migration, and activation of proinflammatory proteins and HMGB1 receptors on HMGB1 activated HUVECs. In the in vivo model, the anti-inflammatory effect of lycopene was assessed by monitoring vascular permeability and migration of leukocytes to the peritoneal cavity of mice injected with lycopene. Lycopene inhibited lipopolysaccharide (LPS)-mediated release of HMGB1, expression of HMGB1-mediated tumor necrosis factor (TNF)-secretory phospholipase A2 (sPLA2)-IIA, and HMGB1-mediated pro-inflammatory signaling responses in endothelial cells. It did this through down-regulation of cell surface expression of cell adhesion molecules (CAMs), HMGB1 receptors, toll-like receptor (TLR)-2, and -4, and receptors for advanced glycation end products (RAGE). These findings suggest that lycopene promotes barrier integrity, inhibits monocyte adhesion and migration to HMGB1 activating HUVECs by blocking activation of proinflammatory cytokines and expression of CAMs and HMGB1 receptors, thereby showing its usefulness as a therapy for vascular inflammatory diseases.
AB - High mobility group box 1 (HMGB1) mediates proinflammatory responses in inflammatory diseases. Lycopene found in tomatoes and tomato products has anti-oxidant, anti-cancer and antiinflammatory effects. The potential anti-inflammatory roles of lycopene in HMGB1-mediated proinflammatory responses in both primary human umbilical vein endothelial cells (HUVECs) and animal were investigated. The anti-inflammatory effects of lycopene were determined including permeability, monocyte adhesion and migration, and activation of proinflammatory proteins and HMGB1 receptors on HMGB1 activated HUVECs. In the in vivo model, the anti-inflammatory effect of lycopene was assessed by monitoring vascular permeability and migration of leukocytes to the peritoneal cavity of mice injected with lycopene. Lycopene inhibited lipopolysaccharide (LPS)-mediated release of HMGB1, expression of HMGB1-mediated tumor necrosis factor (TNF)-secretory phospholipase A2 (sPLA2)-IIA, and HMGB1-mediated pro-inflammatory signaling responses in endothelial cells. It did this through down-regulation of cell surface expression of cell adhesion molecules (CAMs), HMGB1 receptors, toll-like receptor (TLR)-2, and -4, and receptors for advanced glycation end products (RAGE). These findings suggest that lycopene promotes barrier integrity, inhibits monocyte adhesion and migration to HMGB1 activating HUVECs by blocking activation of proinflammatory cytokines and expression of CAMs and HMGB1 receptors, thereby showing its usefulness as a therapy for vascular inflammatory diseases.
KW - HMGB1
KW - Inflammation
KW - Lycopene
KW - Vascular disease
UR - http://www.scopus.com/inward/record.url?scp=84860155576&partnerID=8YFLogxK
U2 - 10.1016/j.fct.2012.03.003
DO - 10.1016/j.fct.2012.03.003
M3 - Article
C2 - 22429818
AN - SCOPUS:84860155576
SN - 0278-6915
VL - 50
SP - 1826
EP - 1833
JO - Food and Chemical Toxicology
JF - Food and Chemical Toxicology
IS - 6
ER -
