The Role of RANTES Signaling on Macrophage Migration and Activation through RANTES-Mediated Glucose Uptake.

• Main Authors: Chien Hung-Che, 簡宏哲
• Other Authors: Hsieh Po-Shiuan
• Format: Others
• Language: zh-TW
• Published: 2014
• Online Access: http://ndltd.ncl.edu.tw/handle/87237961639595267306

碩士 === 國防醫學院 === 生理學研究所 === 102 === Macrophage infiltration and activation plays a critical role in the development of tissue inflammation, especially in obesity-associated adipose tissue inflammation. Chemokine RANTES (also known as CCL5) has been reported to promote macrophage infiltration and its receptor CCR5 is associated with macrophage activation, but the detailed mechanism is unclear. The aim of current study is to investigate the role of RANTES signaling in the regulation of macrophage migration and activation through RANTES-mediated glucose uptake. The present result showed that RANTES increased macrophage migration and glucose uptake in a time and dose dependent manner in RAW cell model. Blockade of glucose uptake by 2-DG significantly inhibited RANTES -induced macrophage migration. RANTES could induce membrane GLUT1 expression as well as phosphorylation of AKT on Thr308、Ser473 and AMPK on Thr172 in RAW cells, but the phosphorylation of p65-NF-κB and ERK was unchanged during the observed period. In addition, inhibition of PI3K、 AMPK and PLC could significantly suppress RANTES-induced macrophage migration and glucose uptake. We also demonstrated that blockade of CCR1 and CCR5 but not CCR3 could inhibit RANTES -induced macrophage glucose uptake and also suppress RANTES -induced macrophage migration. Moreover, Inhibition of PLC and CCR5 could decrease the ability of macrophage migration and glucose uptake in a dose-dependent manner and decrease the phosphorylation of AKT on Thr308、Ser473 and AMPK on Thr172. In THP-1 macrophage cell line, RANTES could increase glucose uptake in M0、M1 and M2 type macrophage. Inhibition of PI3K、AMPK and CCR5 could suppress RANTES-induced macrophage glucose uptake. In respect of macrophage activation, there was not changed in the gene expression of TNF-α、IL-6 and CD206, but IL-10 gene expression was significantly increased after adding RANTES. Besides, the secretion of IL-6 which is M1 type marker was unchanged in treated RANTES group compared to untreated RANTES control. Taken together, the present findings indicate that RANTES could be via CCR5 receptor to activate PLC signaling to increase phosphorylation of PI3K and AMPK thus increase GLUT1 membrane expression. As a result, macrophage glucose uptake was increased and then regulated macrophage migration. However, RANTES didn’t affect the process of macrophage activation.