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- Title
Lysophosphatidylcholine Acetyltransferase 2 (LPCAT2) Influences the Gene Expression of the Lipopolysaccharide Receptor Complex in Infected RAW264.7 Macrophages, Depending on the E. coli Lipopolysaccharide Serotype.
- Authors
Poloamina, Victory Ibigo; Alrammah, Hanaa; Abate, Wondwossen; Avent, Neil D.; Fejer, Gyorgy; Jackson, Simon K.
- Abstract
Simple Summary: E. coli harms over 100 million patients worldwide annually. Its toxin component is lipopolysaccharide, which has various forms, referred to as smooth or rough, based on their structure. Macrophages' main function is to eat up foreign organisms through phagocytosis. This process requires membrane fluidity, which means the phospholipid in the macrophage plasma membrane needs to be regularly remodelled. A lipid-modifying enzyme known as LPCAT2 performs phospholipid remodelling and participates in inflammation. Here, we studied how this enzyme influences the gene expression of receptors that recognise and bind to lipopolysaccharides. These receptors are TLR4, CD14, and MD2. Our results show that LPCAT2 only influenced these receptors when macrophages were infected with smooth lipopolysaccharides. We conclude that LPCAT2 does not influence the gene expression of the receptors in macrophages infected with rough lipopolysaccharides because they do not require lipid-raft microdomains to mediate inflammation, but smooth lipopolysaccharides do. Escherichia coli (E. coli) is a frequent gram-negative bacterium that causes nosocomial infections, affecting more than 100 million patients annually worldwide. Bacterial lipopolysaccharide (LPS) from E. coli binds to toll-like receptor 4 (TLR4) and its co-receptor's cluster of differentiation protein 14 (CD14) and myeloid differentiation factor 2 (MD2), collectively known as the LPS receptor complex. LPCAT2 participates in lipid-raft assembly by phospholipid remodelling. Previous research has proven that LPCAT2 co-localises in lipid rafts with TLR4 and regulates macrophage inflammatory response. However, no published evidence exists of the influence of LPCAT2 on the gene expression of the LPS receptor complex induced by smooth or rough bacterial serotypes. We used RAW264.7—a commonly used experimental murine macrophage model—to study the effects of LPCAT2 on the LPS receptor complex by transiently silencing the LPCAT2 gene, infecting the macrophages with either smooth or rough LPS, and quantifying gene expression. LPCAT2 only significantly affected the gene expression of the LPS receptor complex in macrophages infected with smooth LPS. This study provides novel evidence that the influence of LPCAT2 on macrophage inflammatory response to bacterial infection depends on the LPS serotype, and it supports previous evidence that LPCAT2 regulates inflammatory response by modulating protein translocation to lipid rafts.
- Subjects
ESCHERICHIA coli; GENE expression; LIPID rafts; CELL membranes; MACROPHAGES; MYELOID differentiation factor 88; LIPOPOLYSACCHARIDES
- Publication
Biology (2079-7737), 2024, Vol 13, Issue 5, p314
- ISSN
2079-7737
- Publication type
Article
- DOI
10.3390/biology13050314