Intracellularly Released Cholesterol from Polymer-Based Delivery Systems Alters Cellular Responses to Pneumolysin and Promotes Cell Survival.
Tobias KammannJessica HoffIlknur YildirimBlerina ShkodraTina MüllerChristine WeberMarkus H GrälerUlrich A MausJames C PatonMervyn SingerAnja TraegerUlrich S SchubertMichael BauerAdrian Tibor PressPublished in: Metabolites (2021)
Cholesterol is highly abundant within all human body cells and modulates critical cellular functions related to cellular plasticity, metabolism, and survival. The cholesterol-binding toxin pneumolysin represents an essential virulence factor of Streptococcus pneumoniae in establishing pneumonia and other pneumococcal infections. Thus, cholesterol scavenging of pneumolysin is a promising strategy to reduce S. pneumoniae induced lung damage. There may also be a second cholesterol-dependent mechanism whereby pneumococcal infection and the presence of pneumolysin increase hepatic sterol biosynthesis. Here we investigated a library of polymer particles varying in size and composition that allow for the cellular delivery of cholesterol and their effects on cell survival mechanisms following pneumolysin exposure. Intracellular delivery of cholesterol by nanocarriers composed of Eudragit E100-PLGA rescued pneumolysin-induced alterations of lipid homeostasis and enhanced cell survival irrespective of neutralization of pneumolysin.
Keyphrases
- low density lipoprotein
- escherichia coli
- endothelial cells
- drug delivery
- high glucose
- oxidative stress
- induced apoptosis
- diabetic rats
- pseudomonas aeruginosa
- staphylococcus aureus
- cell death
- drug induced
- cystic fibrosis
- intensive care unit
- cell cycle arrest
- high resolution
- binding protein
- dna binding
- transcription factor
- fatty acid
- biofilm formation
- endoplasmic reticulum stress
- bone regeneration
- community acquired pneumonia