Effect of chronic hypoxia and role of stearoyl-CoA desaturase 1 (SCD1) on the inflammatory response of human primary macrophages

A hypoxic microenvironment in solid tumors frequently is associated with poor outcome due to metabolic adaptation of cells in the tumor microenvironment that supports tumor cells survival and proliferation. However, little is known about how macrophages (MФ) metabolically and phenotypically adapt to chronic hypoxia (CH) and how this in turn affects tumor-associated inflammation. Here, we subjected MФs to CH to compare their inflammatory phenotype with normoxic MФs. In addition, we transfected SCD1, the rate-limiting enzyme of fatty acid desaturation, to investigate its role in MФ adaptation to oxygen shortage and its contribution to the inflammatory function. Human primary macrophages under chronic hypoxia (1% oxygen for 5 days) and normoxia (21% oxygen) with and without stearoyl-CoA desaturase (SCD1) or control and harvested 5 days after transfection (n = 6).

实体瘤的低氧微环境常与不良预后相关，其机制为肿瘤微环境内细胞的代谢适应可支持肿瘤细胞的存活与增殖。然而，目前对于巨噬细胞（macrophages, MФ）如何在代谢与表型层面适应慢性缺氧（chronic hypoxia, CH），以及该过程反过来如何影响肿瘤相关炎症，我们仍知之甚少。本研究将巨噬细胞暴露于慢性缺氧环境，以对比其与常氧培养巨噬细胞的炎症表型。此外，我们转染了作为脂肪酸去饱和限速酶的硬脂酰辅酶A去饱和酶1（stearoyl-CoA desaturase 1, SCD1），以探究其在巨噬细胞适应缺氧环境过程中的作用，及其对炎症功能的贡献。本实验采用原代人巨噬细胞，分别置于慢性缺氧（1%氧浓度，持续5天）与常氧（21%氧浓度）环境中培养，并转染硬脂酰辅酶A去饱和酶（SCD1）或对照载体，于转染后5天收集样本，每组样本量n=6。