Knockdown of Transmembrane Protein 150A (TMEM150A) Results in Increased Production of Multiple Cytokines.

Abstract

Lipopolysaccharide (LPS)-induced signaling through Toll-like receptor 4 (TLR4) is mediated by the plasma membrane lipid, phosphatidylinositol (4,5)-bisphosphate [PI(4,5)P2] and its derivatives diacylglycerol and inositol trisphosphate. Levels of PI(4,5)P2 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)P2 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.