The effects of 15-keto-PGE2 on IL-10 production in human macrophages

• Main Authors: Kuan-Hsun Chen, 陳冠勳
• Other Authors: Lee-Ming Chuang
• Format: Others
• Language: en_US
• Published: 2009
• Online Access: http://ndltd.ncl.edu.tw/handle/92631803767634213843

碩士 === 國立臺灣大學 === 分子醫學研究所 === 97 === Type 2 diabetes (T2D) mellitus is currently one of the main health treats for humans. It is now broadly accepted that low-grade chronic inflammation associated with obesity leads to the onset of type 2 diabetes. Obesity-associated inflammation is characterized by an increased abundance of macrophages in adipose tissue along with the production of inflammatory cytokines. Interleuikin-10 (IL-10) is a pleiotropic cytokine that mediate immune and inflammatory responses by inhibiting the synthesis of pro-inflammatory cytokines. IL-10 secreted from macrophages in adipose tissue may counteract the inflammatory effects and protect adipose tissue from injuring. In this study, by using PMA-differentiated THP-1 macrophages, we demonstrated that 15-keto-PGE2 could induce the anti-inflammatory cytokine IL-10 production, but not the pro-inflammatory cytokines (TNF-α, IL-6 and IL-12). The capacity of 15-keto-PGE2 to elevate IL-10 expression level was mediated through PI3K/AKT/GSK-3β signaling pathway. 15-keto-PGE regulated IL-10 promoter activation by increasing the binding activities of transcription factors, CREB and Sp1. Furthermore, 15-keto-PGE2 also induced IL-10 production through partial PPARγ-dependent pathway. Taken together, these findings explore the crucial role of 15-keto-PGE2 in anti-inflammatory effect and enforce the importance of PGE2 catabolism in the immune response.