Interleukin-24 Suppresses the Growth of Vascular Smooth Muscle Cells by Inhibiting H2O2-Induced Reactive Oxygen Species Production
| Autor: | Hyung-Sik Kang, Ki-Mo Lee, Min-Ji Song, Min Park, Jae-Wook Oh, Hwa-Youn Lee, Haeng-A. Kang, Kisung Ko |
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| Rok vydání: | 2012 |
| Předmět: | |
| Zdroj: | Pharmacology. 90:332-341 |
| ISSN: | 1423-0313 0031-7012 |
| Popis: | Background/Aim: The abnormal growth of vascular smooth muscle cells (VSMCs) induced by reactive oxygen species (ROS) is considered a major pathogenic process in vascular diseases. Interleukin (IL)-24 specifically inhibits cancer cell growth through the induction of cell cycle arrest and apoptosis. However, the role of IL-24 in ROS-induced VSMC growth has not yet been investigated. Methods: An MTT assay, gene expression analysis, flow cytometry and a scratch wound healing assay were performed to determine the anti-growth effects of IL-24 in H2O2-treated mouse vascular aortic smooth muscle (MOVAS) cells. To elucidate the effect of IL-24 on ROS-induced signaling, Western blot analysis was employed. Results: IL-24 inhibited the growth of normal MOVAS cells treated with H2O2 by inducing a cell cycle arrest at the G₀/G1 phase through the regulation of p21 and cyclin D1. Furthermore, IL-24 suppressed mRNA expression of vascular endothelial growth factor and platelet-derived growth factor and subsequently decreased the level of cell migration in response to H2O2. Interestingly, IL-24 attenuated the H2O2-induced ROS production by reducing the mitochondrial H2O2 production and enhancing the expression of antioxidant enzymes. We also showed that the ability of H2O2 to induce the PI3K/Akt and Erk signaling pathways was blocked by IL-24. Conclusion: These findings suggest a novel mechanism in which IL-24 suppresses the growth of normal VSMCs by inhibiting H2O2-induced ROS production through the regulation of mitochondrial ROS production and expression of antioxidant enzymes. |
| Databáze: | OpenAIRE |
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