Analysis of the role of signaling suppressor SOCS3 in the development of atherosclerosis

2005 Fiscal Year Final Research Report Summary

• Project/Area Number: 16590723
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Circulatory organs internal medicine
• Research Institution: Kurume University
• Principal Investigator: YASUKAWA Hideo Kurume University, Cardiovascular Research institute, Assistant Professor, 循環器病研究所, 講師 (60289361)
• Co-Investigator(Kenkyū-buntansha): IMAIZUMI Tsutomu Kurume University, School of Medicine, Professor, 医学部, 教授 (60148947) ; KAI Hisashi Kurume University, School of Medicine, Associate Professor, 医学部, 助教授 (60281531)
• Project Period (FY): 2004 – 2005
• Keywords: atherosclerosis / macrophage / SOCS / STAT3 / Interleukin-6

Research Abstract

STAT3 was phosphorylated in the aorta from ApoE deficient mice on high fat diet. On the other hand, phosphorylation of STAT3 was not observed in the aorta from control mice. Immunostatining revealed that STAT3 were mainly phosphorylated in macrophages and endothelial cells of plaque from ApoE deficient mice on high fat diet. RT-PCR analysis showed that IL-6, oncostatin M and SOCS3 (suppressor of cytokine signaling) were significantly induced in aorta from Apo deficient mice compared with wild type mice. LIF(leukemia inhibitory factor) and IL-10 were not expressed in control mice and ApoE deficient mice. These results suggest that gp130 cytokines IL-6 and oncostatin M activate JAK-STAT3 pathway that is negatively regulated by SOCS3. To evaluate the role of IL-6 on foam cell formation of macrophages, we examined the effect of IL-6 on oxidized-LDL (oxLDL) uptake by murine peritoneal macrophages in vitro. IL-6 stimulation significantly increased the incorporation of Dil-labeled oxLDL of macrophages. These data suggest that IL-6-STAT3 pathway is activated during the development of atherosclerosis and may contribute to foam cell formation of macrophages.