P049 Interleukin-10 family of cytokines suppresses growth of vascular smooth muscle cells by inhibiting ROS production via PI3K/AKT and ERK signaling pathways

Introduction The abnormal growth of vascular smooth muscle cells induced by reactive oxygen species is considered as a major pathogenic process in vascular diseases. Interleukin-10 family of cytokines is known to inhibit cancer cell growth through induction of cell cycle arrest and apoptosis. However, the role of interleukin-10 family of cytokines in ROS-induced VSMC growth has not been investigated yet. Methods Mouse vascular aorta smooth muscle cells were treated with H 2 O 2 . The cell cycle and intracellular ROS production was examined using flow cytometry analysis, and mRNA expression of VEGF and PDGF was investigated by RT-PCR and Real time PCR. Protein expression of PI3K/Akt and Erk was determined by western blot analysis Results We found that interleukin-10 family of cytokines inhibited the growth of mouse vascular aorta smooth muscle cells treated with H 2 O 2 by inducing the arrest of cell cycle at G0/G1 phase through the regulation of p21 and cyclin D1. Furthermore, interleukin-10 family of cytokines suppressed the mRNA expression of VEGF and PDGF, which subsequently reduced an elevated level of migration in response to H 2 O 2 . Interestingly, interleukin-10 family of cytokines attenuated H 2 O 2 -induced ROS production due to the upregulated mRNA expression of TRX-1 and PRX-2. Signaling through protein tyrosine kinases and mitogen-activated protein kinases is required for ROS-mediated activation of VSMCs. Consistently, we also showed that H 2 O 2 -induced PI3K/Akt and Erk signaling pathways were blocked by interleukin-10 family of cytokines. Conclusion Our data suggest a novel mechanism that interleukin-10 family of cytokines suppresses growth of normal VSMCs stimulated by H 2 O 2 through inhibiting ROS production via PI3K/Akt and Erk signaling pathways.