Insulin regulates monocyte trans-endothelial migration through surface expression of macrophage-1 antigen

BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE

卷:1842

Article

Jin, Seo Yeon^1,2  Kim, Eun Kyoung^1,2  Ha, Jung Mm^1,2  Lee, Dong Hyung³  Kim, Jeong Su⁴  Kim, Il Young⁵  Song, Sang Heon⁵  Shin, Hwa Kyoung⁶  Kim, Chi Dae^1,2  Bae, Sun Sik^1,2 

[1] Pusan Natl Univ, Sch Med, MRC Ischem Tissue Regenerat, Med Res Inst, Yangsan 626870, Kyungnam, South Korea

[2] Pusan Natl Univ, Sch Med, Dept Pharmacol, Yangsan 626870, Kyungnam, South Korea

[3] Pusan Natl Univ, Sch Med, Dept Obstet & Gynecol, Yangsan 626870, Kyungnam, South Korea

[4] Pusan Natl Univ, Sch Med, Pusan Natl Univ Hosp, Cardiovasc Dis Ctr, Yangsan 626870, Kyungnam, South Korea

[5] Pusan Natl Univ, Sch Med, Pusan Natl Univ Hosp, Dept Internal Med, Yangsan 626870, Kyungnam, South Korea

[6] Pusan Natl Univ, Sch Korean Med, Dept Anat, Yangsan 626870, Kyungnam, South Korea

关键词: PI3K;    Akt;    Migration;    Adhesion;    Monocyte infiltration;   

DOI  :  10.1016/j.bbadis.2014.06.003

来源: Elsevier

【 摘 要 】

During the pathogenesis of atherosclerosis, adhesion of monocytes to vascular endothelium and subsequent migration across the endothelium has been recognized as a key process in the chronic inflammatory response in atherosclerosis. As type 2 diabetes is closely associated with the pathogenesis of atherosclerosis, we investigated whether monocyte adhesion and migration were affected by insulin. We found that insulin activated Akt and induced subsequent migration in THP-1. However, glucose and insulin-like growth factor-1, which is a growth factor that is structurally similar to insulin, were not effective. Insulin-dependent migration of THP-1 was blocked by inhibition of PI3K or Akt and by silencing of Akt1. Insulin-dependent migration of bone marrow-derived monocytic cells (BDMCs) was attenuated by inhibition of PI3K and Akt In addition, BDMCs from Akt1(-/-) mice showed defects in insulin-dependent migration. Stimulation of THP-1 with insulin caused adhesion with human vein endothelial cells (HUVECs) that was blocked by silencing of Akt1. However, stimulation of HUVECs did not cause adhesion with THP-1. Moreover, BDMCs from Akt1(-/-) mice showed defects in insulin-dependent adhesion with HUVECs. Insulin induced surface expression of Mac-1, and neutralization of Mac-1 blocked insulin-induced adhesion of THP-1 as well as BDMCs. Surface expression of Mac-1 was blocked in THP-1 with silenced Akt1, and in BDMCs isolated from mice lacking Akt1. Finally, trans-endothelial migration of THP-1 and BDMCs was blocked by Mac-l-neutralizing antibody, in THP-1 with silenced Akt1 and in BDMCs from Akt1(-/-) mice. These results suggest that insulin stimulates monocyte trans-endothelial migration through Akt-dependent surface expression of Mac-1, which may be part of the atherogenesis in type 2 diabetes. (C) 2014 Elsevier B.V. All rights reserved.

【 授权许可】

Free