Department of Biology and Wildlife, College of Natural Science and Mathematics, University of Alaska Fairbanks, Fairbanks, AK 99775, USA.
Department of Pharmacology and Toxicology, Faculty of Veterinary Medicine, University of Warmia and Mazury in Olsztyn, Oczapowskiego 13, 10-718 Olsztyn, Poland.
Biomolecules. 2023 Apr 29;13(5):770. doi: 10.3390/biom13050770.
This study investigated the critical role of Glut1-mediated glucose metabolism in the inflammatory response of macrophages, which are energy-intensive cells within the innate immune system. Inflammation leads to increased Glut1 expression, ensuring sufficient glucose uptake to support macrophage functions. We demonstrated that using siRNA to knock down Glut1 reduces the expression of various pro-inflammatory cytokines and markers, such as IL-6, iNOS, MHC II/CD40, reactive oxygen species, and the hydrogen sulfide (HS)-producing enzyme cystathionine γ-lyase (CSE). Glut1 activates a pro-inflammatory profile through a nuclear factor (NF)-κB, while silencing Glut1 can prevent lipopolysaccharide (LPS)-induced IκB degradation, blocking NF-κB activation. Glut1's role in autophagy, an essential process for macrophage functions such as antigen presentation, phagocytosis, and cytokine secretion, was also measured. The findings show that LPS stimulation decreases autophagosome formation, but Glut1 knockdown reverses this effect, increasing autophagy beyond control levels. The study highlights Glut1's importance in macrophage immune responses and its regulation of apoptosis during LPS stimulation. Knocking down Glut1 negatively impacts cell viability and mitochondrial intrinsic pathway signaling. These findings collectively suggest that targeting macrophage glucose metabolism through Glut1 could potentially serve as a target for controlling inflammation.
本研究探讨了 Glut1 介导的葡萄糖代谢在巨噬细胞炎症反应中的关键作用，巨噬细胞是先天免疫系统中能量需求较高的细胞。炎症导致 Glut1 表达增加，以确保有足够的葡萄糖摄取来支持巨噬细胞功能。我们证明，使用 siRNA 敲低 Glut1 可降低各种促炎细胞因子和标志物的表达，如 IL-6、iNOS、MHC II/CD40、活性氧和产生硫化氢（HS）的酶胱硫醚γ-裂解酶（CSE）。Glut1 通过核因子（NF）-κB 激活促炎表型，而沉默 Glut1 可以阻止脂多糖（LPS）诱导的 IκB 降解，从而阻断 NF-κB 激活。还测量了 Glut1 在自噬中的作用，自噬是巨噬细胞功能（如抗原呈递、吞噬和细胞因子分泌）所必需的过程。研究结果表明，LPS 刺激会减少自噬体的形成，但 Glut1 敲低可逆转这种效应，使自噬超过对照水平。该研究强调了 Glut1 在巨噬细胞免疫反应中的重要性及其在 LPS 刺激期间对细胞凋亡的调节作用。敲低 Glut1 会对细胞活力和线粒体内在途径信号产生负面影响。这些发现共同表明，通过 Glut1 靶向巨噬细胞葡萄糖代谢可能成为控制炎症的一个靶点。
