Park Bongkyun, Yim Joung-Han, Lee Hong-Kum, Kim Byung-Oh, Pyo Suhkneung
a School of Pharmacy , Sungkyunkwan University , Suwon , Republic of Korea.
Biosci Biotechnol Biochem. 2015;79(4):539-52. doi: 10.1080/09168451.2014.991681. Epub 2014 Dec 15.
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.
细胞黏附分子在炎症过程和动脉粥样硬化中起着关键作用。在本研究中，我们研究了来自南极地衣Ramalina terebrata的一种化合物——松萝酸对肿瘤坏死因子-α（TNF-α）诱导血管平滑肌细胞（VSMCs）中血管细胞黏附分子-1（VCAM-1）表达的影响。用松萝酸（0.1 - 10μg/mL）预处理VSMCs可浓度依赖性地抑制TNF-α诱导的VCAM-1表达。此外，松萝酸抑制THP-1（人急性单核细胞白血病细胞系）细胞与TNF-α刺激的VSMCs的黏附。松萝酸抑制TNF-α诱导的活性氧（ROS）生成、肽酰精氨酸脱亚氨酶4（PADI4）表达以及p38、细胞外信号调节激酶（ERK）和c-Jun氨基末端激酶（JNK）的磷酸化。此外，松萝酸抑制TNF-α诱导的核因子κB（NF-κB）和活化蛋白-1（AP-1）的易位。用小干扰RNA或PADI4特异性抑制剂抑制PADI4表达可显著减弱TNF-α诱导的VSMCs中NF-κB和AP-1的活化以及VCAM-1的表达。我们的研究深入了解了松萝酸活性的潜在机制，并表明松萝酸可能是调节动脉粥样硬化炎症的潜在治疗药物。
