Buitenhuis, Egbert Henri (2025) The potential role of LPS dephosphorylation in preventing Necrotizing Enterocolitis. Master's Research Project 1, Biomedical Sciences.
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Abstract
Necrotizing enterocolitis (NEC) is a severe intestinal disease in preterm infants, driven by lipopolysaccharide (LPS) from gram-negative bacteria activating Toll-like receptor 4 (TLR4). TLR4 signals through pro-inflammatory MyD88 and less inflammatory TRIF pathways, and shifting this balance may help prevent NEC. We tested the effects of LPS, diphosphoryl lipid A (DPLA), and its dephosphorylated form monophosphoryl lipid A (MPLA) on epithelial barrier integrity and TLR4 signaling. CaCo2 and IEC6 epithelial cells were stimulated and analyzed for tight junction proteins, showing no significant disruption even at high LPS levels. To study signaling, RAW 264.7 macrophages were treated and cytokine expression measured by qPCR. MPLA induced higher TRIF-associated and lower MyD88-associated cytokines compared to DPLA. Thus, LPS dephosphorylation reduces pro-inflammatory TLR4 signaling, potentially limiting intestinal injury and supporting NEC prevention strategies.
| Item Type: | Thesis (Master's Research Project 1) |
|---|---|
| Supervisor name: | Poelstra, K. |
| Degree programme: | Biomedical Sciences |
| Thesis type: | Master's Research Project 1 |
| Language: | English |
| Date Deposited: | 09 Sep 2025 07:20 |
| Last Modified: | 09 Sep 2025 07:20 |
| URI: | https://fse.studenttheses.ub.rug.nl/id/eprint/36999 |
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