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Inhibition of VCAM-1 expression on mouse vascular smooth muscle cells by lobastin via downregulation of p38, ERK 1/2 and NF-κB signaling pathways

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Abstract

Atherosclerosis is a chronic inflammatory disease, the progression of which is associated with the increased expression of cell adhesion molecules on vascular smooth muscle cells (VSMCs). Lobastin is a new pseudodepsidone isolated from Stereocaulon alpinum, Antarctic lichen, which is known to have antioxidant and antibacterial activities. However, the nature of the biological effects of lobastin still remains unclear. In the present study, we examine the effect of lobastin on the expression of vascular cell adhesion molecules (VCAM-1) induced by TNF-α in the cultured mouse VSMC cell line, MOVAS-1. Pretreatment of VSMCs for 2 h with lobastin (0.1–10 μg/ml) concentration-dependently inhibited TNF-α-induced protein expression of VCAM-1. Lobastin also inhibited TNF-α-induced production of intracellular reactive oxygen species (ROS). Lobastin abrogated TNF-α-induced phosphorylation of p38 and ERK 1/2, but not JNK, and also inhibited TNF-α-induced NK-κB activation. In addition, lobastin suppressed TNF-α-induced IκB kinase activation, subsequent degradation of IκBα and nuclear translocation of p65 NF-κB. Our results indicate that lobastin downregulates the TNF-α-mediated induction of VCAM-1 in VSMC by inhibiting the p38, ERK 1/2 and NF-κB signaling pathways and intracellular ROS generation. Thus, lobastin may be an important regulator of inflammation in the atherosclerotic lesion and a novel therapeutic drug for the treatment of atherosclerosis.

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Acknowledgments

This research was supported by the grant of the Ministry of Oceans and Fisheries’ R&D project (PM13030) and the Korea Polar Research Institute (KOPRI) project (PE13040).

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Authors and Affiliations

  1. School of Pharmacy, Sungkyunkwan University, Suwon City, Gyeonggi-do, 440-746, South Korea

    Kyoungran Lee & Suhkneung Pyo

  2. Polar BioCenter, Korea Polar Research Institute, KORDI, Incheon, Republic of Korea

    Joung-Han Yim & Hong-Kum Lee

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  1. Kyoungran Lee
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Correspondence to Suhkneung Pyo.

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Lee, K., Yim, JH., Lee, HK. et al. Inhibition of VCAM-1 expression on mouse vascular smooth muscle cells by lobastin via downregulation of p38, ERK 1/2 and NF-κB signaling pathways. Arch. Pharm. Res. 39, 83–93 (2016). https://doi.org/10.1007/s12272-015-0687-3

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