Interleukin-24 suppresses the growth of vascular smooth muscle cells by inhibiting H(2)O(2)-induced reactive oxygen species production.
OBJECTIVE
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 H(2)O(2)-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 H(2)O(2) by inducing a cell cycle arrest at the G(0)/G(1) 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 H(2)O(2). Interestingly, IL-24 attenuated the H(2)O(2)-induced ROS production by reducing the mitochondrial H(2)O(2) production and enhancing the expression of antioxidant enzymes. We also showed that the ability of H(2)O(2) to induce the PI3K/Akt and Erk signaling pathways was blocked by IL-24.


CONCLUSIONS
These findings suggest a novel mechanism in which IL-24 suppresses the growth of normal VSMCs by inhibiting H(2)O(2)-induced ROS production through the regulation of mitochondrial ROS production and expression of antioxidant enzymes.
School of Biological Sciences and Technology, Chonnam National University, Gwangju, Republic of Korea.
Ki-Mo
KM
Lee
Haeng-A
HA
Kang
Min
M
Park
Hwa-Youn
HY
Lee
Min-Ji
MJ
Song
Kisung
K
Ko
Jae-Wook
JW
Oh
Hyung-Sik
HS
Kang
D000818:Animals; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D007378:Interleukins / Q000502:physiology*; D051379:Mice; D008928:Mitochondria / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000166:cytology; D032389:Myocytes, Smooth Muscle / Q000502:physiology*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism*; D000099180:Interleukin-24
D048049:Extracellular Signal-Regulated MAP Kinases; D007378:Interleukins; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D017382:Reactive Oxygen Species; D000099180:Interleukin-24