Evaluating the endothelial-microglial interaction and comprehensive inflammatory marker profiles under acute exposure to ultrafine diesel exhaust particles in vitro
| Autor: | Gabriel J. Odom, Fan Zhang, Erica D. Bruce, Amjad Dabi, Grace V. Aquino |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Chemokine medicine.medical_treatment Inflammation Pharmacology Toxicology Blood–brain barrier medicine.disease_cause complex mixtures 03 medical and health sciences 0302 clinical medicine medicine Animals Particle Size Cells Cultured Vehicle Emissions chemistry.chemical_classification Reactive oxygen species Microglia biology Chemistry Endothelial Cells Coculture Techniques Rats 030104 developmental biology medicine.anatomical_structure Cytokine Blood-Brain Barrier Toxicity biology.protein Particulate Matter medicine.symptom Reactive Oxygen Species 030217 neurology & neurosurgery Oxidative stress |
| Zdroj: | Toxicology. 454:152748 |
| ISSN: | 0300-483X |
| Popis: | Exposure to combustion-derived particulate matter (PM) such as diesel exhaust particles (DEP) is a public health concern because people in urban areas are continuously exposed, and once inhaled, fine and ultrafine DEP may reach the brain. The blood-brain barrier (BBB) endothelial cells (EC) and the perivascular microglia protect the brain from circulating pathogens and neurotoxic molecules like DEP. While the BBB-microglial interaction is critical for maintaining homeostasis, no study has previously evaluated the endothelial-microglial interaction nor comprehensively characterized these cells’ inflammatory marker profiles under ultrafine DEP exposures in vitro. Therefore, the goal of this study was to investigate the in vitro rat EC-microglial co-culture under acute (24 h.) exposure to ultrafine DEP (0.002–20 μg/mL), by evaluating key mechanisms associated with PM toxicity: lactate dehydrogenase (LDH) leakage, reactive oxygen species (ROS) generation, cell metabolic activity (CMA) changes, and production of 27 inflammatory markers. These parameters were also evaluated in rat microglial and endothelial monocultures to determine whether the EC-microglial co-culture responded differently than the cerebrovasculature and microglia alone. While results indicated that ultrafine DEP exposure caused concentration-dependent increases in LDH leakage and ROS production in all groups, as expected, exposure also caused mixed responses in CMA and atypical cytokine/chemokine profiles in all groups, which was not expected. The inflammation assay results further suggested that the microglia were not classically activated under this exposure scenario, despite previous in vitro studies showing microglial activation (priming) at similar concentrations of ultrafine DEP. Additionally, compared to the cerebrovasculature alone, the EC-microglia interaction in the co-culture did not appear to cause changes in any parameter save in pro-inflammatory marker production, where the interaction appeared to cause an overall downregulation in cytokine/chemokine levels after ultrafine DEP exposure. Finally, to our knowledge, this is the first study to evaluate the influence of microglia on the BBB’s ultrafine DEP-induced cytotoxic and inflammatory responses, which are heavily implicated in the pathogenesis of PM-related cerebrovascular dysfunction and neurodegeneration. |
| Databáze: | OpenAIRE |
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