Modulation of adhesion molecules and monocyte chemoattractant protein by tumor necrosis factor-alpha and salicylic acid in primary human coronary artery endothelial cells.
Kawasaki disease (KD) is an illness characterized by vascular inflammation of coronary arteries leading to coronary aneurysms and thromboses. Infiltration of immune cells into the intima and adventitia are observed in autopsy tissues of patients with KD. Using semi-quantitative RT-PCR and cell-based ELISA, we demonstrated that tumor necrosis factor-a induced the expression of intercellular adhesion molecules-1 and E-selectin, as well as monocyte chemoattractant protein-1, in a time- and dose-dependent manner in primary human coronary artery endothelial cell cultures. This increase was inhibited by salicylic acid (NaSal), and involved the transcription factor NF-kappaB. Based on these data, we suggest a pathogenetic mechanism for KD, whereby immune cells are attracted to sites of inflammation, undergo extravasation, release enzymes that assist in vascular remodeling, thereby weakening the endothelium and hastening the process of aneurysm formation. NaSal, in addition to preventing thrombosis and lowering fever in KD, may also function in down-regulating adhesion molecules during the inflammatory stage of KD.
Chua
P K
PK
Retrovirology Research Laboratory, Pacific Biomedical Research Center, Leahi Hospital, Atherton Building, 3675 Kilauea Avenue, Honolulu, HI 96816, USA.
Yanagihara
R
R
Melish
M E
ME
Nerurkar
V R
VR
D015815:Cell Adhesion Molecules / Q000378:metabolism*; D002478:Cells, Cultured; D003331:Coronary Vessels / Q000187:drug effects / Q000378:metabolism*; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D018945:Monocyte Chemoattractant Proteins / Q000378:metabolism*; D009080:Mucocutaneous Lymph Node Syndrome / Q000378:metabolism*; D020156:Salicylic Acid / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D015815:Cell Adhesion Molecules; D018945:Monocyte Chemoattractant Proteins; D014409:Tumor Necrosis Factor-alpha; D020156:Salicylic Acid