Ramalin inhibits VCAM-1 expression and adhesion of monocyte to vascular smooth muscle cells through MAPK and PADI4-dependent NF-kB and AP-1 pathways

• Published in: Bioscience, Biotechnology, and Biochemistry
• Main Authors: Park, Bongkyun, Yim, Joung-Han, Lee, Hong-Kum, Kim, Byung-Oh, Pyo, Suhkneung
• Other Authors: the Korea Polar Research Institute
• Format: Article in Journal/Newspaper
• Language: English
• Published: Oxford University Press (OUP) 2015
• Subjects: Organic Chemistry; Molecular Biology; Applied Microbiology and Biotechnology; General Medicine; Biochemistry; Analytical Chemistry; Biotechnology; Antarctic; The Antarctic; Antarc*
• Online Access: http://dx.doi.org/10.1080/09168451.2014.991681; http://academic.oup.com/bbb/article-pdf/79/4/539/36806684/bbb0539.pdf

Abstract Cell adhesion molecules play a critical role in inflammatory processes and atherosclerosis. In this study, we investigated the effect of ramalin, a chemical compound from the Antarctic lichen Ramalina terebrata, on vascular cell adhesion molecule-1 (VCAM-1) expression induced by TNF-α in vascular smooth muscular cells (VSMCs). Pretreatment of VSMCs with ramalin (0.1–10 μg/mL) concentration-dependently inhibited TNF-α-induced VCAM-1 expression. Additionally, ramalin inhibited THP-1 (human acute monocytic leukemia cell line) cell adhesion to TNF-α-stimulated VSMCs. Ramalin suppressed TNF-α-induced production of reactive oxygen species (ROS), PADI4 expression, and phosphorylation of p38, ERK, and JNK. Moreover, ramalin inhibited TNF-α-induced translocation of NF-κB and AP-1. Inhibition of PADI4 expression by small interfering RNA or the PADI4-specific inhibitor markedly attenuated TNF-α-induced activation of NF-κB and AP-1 and VCAM-1 expression in VSMCs. Our study provides insight into the mechanisms underlying ramalin activity and suggests that ramalin may be a potential therapeutic agent to modulate inflammation within atherosclerosis.