Department of Molecular Biomedical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, North Carolina, USA.
Center for Human Health and the Environment, North Carolina State University, Raleigh, North Carolina, USA.
J Interferon Cytokine Res. 2022 Jul;42(7):336-342. doi: 10.1089/jir.2022.0063.
Lipopolysaccharide (LPS)-induced signaling through Toll-like receptor 4 (TLR4) is mediated by the plasma membrane lipid, phosphatidylinositol (4,5)-bisphosphate [PI(4,5)P] and its derivatives diacylglycerol and inositol trisphosphate. Levels of PI(4,5)P are controlled enzymatically and fluctuate in LPS-stimulated cells. Recently, transmembrane protein 150A (TMEM150A/TM6P1/damage-regulated autophagy modulator 5) has been shown to regulate PI(4,5)P production at the plasma membrane by modifying the composition of the phosphatidylinositol 4-kinase enzyme complex. To determine if TMEM150A function impacts TLR4 signaling, TMEM150A was knocked down in TLR4-expressing epithelial cells and cytokine expression quantified after LPS stimulation. In general, decreased expression of TMEM150A led to increased levels of LPS-induced cytokine secretion and transcript levels. Unexpectedly, knockdown of TMEM150A in a lung epithelial cell line (H292) also led to increased cytokine levels in the unstimulated conditions suggesting TMEM150A plays an important role in cellular homeostasis. Future studies will investigate if TMEM150A plays a similar role for other TLR agonists and in other cell lineages.
脂多糖（LPS）通过 Toll 样受体 4（TLR4）诱导的信号转导由质膜脂质磷脂酰肌醇（4,5）-二磷酸[PI（4,5）P]及其衍生物二酰基甘油和肌醇三磷酸介导。PI（4,5）P 的水平通过酶控制并在 LPS 刺激的细胞中波动。最近，跨膜蛋白 150A（TMEM150A/TM6P1/损伤调节自噬调节剂 5）已被证明通过修饰磷脂酰肌醇 4-激酶酶复合物的组成来调节质膜上的 PI（4,5）P 产生。为了确定 TMEM150A 功能是否影响 TLR4 信号转导，在 TLR4 表达的上皮细胞中敲低 TMEM150A，并在 LPS 刺激后定量细胞因子表达。一般来说，TMEM150A 的表达降低导致 LPS 诱导的细胞因子分泌和转录水平增加。出乎意料的是，在肺上皮细胞系（H292）中敲低 TMEM150A 也导致未刺激条件下细胞因子水平升高，这表明 TMEM150A 在细胞稳态中发挥重要作用。未来的研究将调查 TMEM150A 是否在其他 TLR 激动剂和其他细胞谱系中发挥类似作用。
