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Published on: January 7, 2019
Knockdown of Transmembrane Protein 150A (TMEM150A) Results in Increased Production of Multiple Cytokines
Jessica L Romanet1, Katherine L Cupo1, Jeffrey A Yoder1,2,3
1Department of Molecular Biomedical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, North Carolina, USA.
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.
Insights
Transmembrane protein 150A regulates phosphatidylinositol (4,5)-bisphosphate levels, impacting Toll-like receptor 4 signaling. Decreased TMEM150A expression enhances lipopolysaccharide-induced cytokine production, affecting cellular homeostasis.
Area of Science:
- Immunology
- Cell Biology
- Molecular Biology
Background:
- Lipopolysaccharide (LPS) signals via Toll-like receptor 4 (TLR4), involving the lipid phosphatidylinositol (4,5)-bisphosphate [PI(4,5)P2].
- PI(4,5)P2 levels are dynamically regulated and crucial for LPS-induced signaling.
- Transmembrane protein 150A (TMEM150A) modulates PI(4,5)P2 production by affecting phosphatidylinositol 4-kinase complexes.
Purpose of the Study:
- To investigate the role of TMEM150A in regulating TLR4 signaling.
- To determine how TMEM150A knockdown affects cytokine expression in response to LPS.
Main Methods:
- TMEM150A was knocked down in TLR4-expressing epithelial cells.
- Cytokine expression (secretion and transcript levels) was quantified after LPS stimulation.
- Experiments included unstimulated and stimulated conditions in a lung epithelial cell line (H292).
Main Results:
- Reduced TMEM150A expression generally increased LPS-induced cytokine secretion and transcript levels.
- Unexpectedly, TMEM150A knockdown in H292 cells also elevated cytokine levels without LPS stimulation.
- This suggests TMEM150A influences basal cellular homeostasis.
Conclusions:
- TMEM150A plays a significant role in modulating TLR4-mediated inflammatory responses.
- TMEM150A is implicated in maintaining cellular homeostasis, independent of LPS stimulation.
- Further research is warranted to explore TMEM150A's function with other TLR agonists and cell types.
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