Effects of G6PD Deficiency on the Signal 1 Pathway of Inflammasome Activation

• Main Authors: Jih Hsiang Ko, 柯日翔
• Other Authors: T. Y. Chiu
• Format: Others
• Language: zh-TW
• Published: 2016
• Online Access: http://ndltd.ncl.edu.tw/handle/t8snea

碩士 === 長庚大學 === 醫學生物技術暨檢驗學系 === 104 === Glucose-6-phosphate dehydrogenase (G6PD) is an important enzyme in maintaining cellular redox homeostasis and regulating immune response. NLRP3 inflammasome, a component of innate immunity, is a multiprotein complex consisting of NOD-like receptor, ASC and pro-caspase-1. Activation of caspase-1 causes the cleavage of pro-interleukin 1-beta (pro-IL-1β) to mature IL-1β and then release to extracellular fluid to recruit immune cells against pathogens. However, whether G6PD status affects NLRP3 inflammasome activation remains unclear. Our previous studies have show that decreased IL-1β secretion has been found in G6PD-deficient macrophages. In our current study, similar phenomenon was observed in G6PD-knockdown (G6PD-kd) THP-1 macrophages. The transcriptional and translational levels of pro-IL-1β were attenuated in G6PD-kd THP-1 macrophages. However, the expression of pro-IL-1β was significantly different upon PMA treatment in these two cells. Therefore, THP-1 monocytes was first differentiated by PMA pretreatment, followed by siG6PD knockdown and inflammasome activation. The secretion of IL-1β and the expression of pro-IL-1β were decreased in G6PD-knockdown (siG6PD) THP-1 macrophages. Furthermore, the upstream phosphorylation level of NF-B was attenuated in siG6PD THP-1 macrophages. These findings suggest that G6PD participates in the activation of NLRP3 inflammasome via NF-B signaling.