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Extracellular vesicles from PBDE-47 treated M(LPS) THP-1 macrophages modulate the expression of markers of epithelial integrity, EMT, inflammation and muco-secretion in ALI culture of airway epithelium. | LitMetric

AI Article Synopsis

  • The study investigates how PBDE-47 affects microRNA in macrophage-derived small extracellular vesicles (sEVs) and its impact on lung epithelial cells (A549) as a defense barrier.
  • Analysis techniques included nanoparticle tracking and qPCR to assess sEVs' microRNA and mRNA expression related to tight junctions and inflammation in A549 cells.
  • Key findings reveal that PBDE-47 alters microRNA profiles in sEVs, which in turn influences the expression of critical mRNA related to lung epithelial function, potentially leading to lung disease.

Article Abstract

Aims: The lung epithelial cells form a physical barrier to the external environment acting as the first line of defence against potentially harmful environmental stimuli. These cells interact with several other cellular components, of which macrophages are some of the most relevant. We analysed the effects of the PBDE-47 on the microRNA cargo of THP-1 macrophage like derived small Extracellular Vesicles (sEVs) and the effects on A549 lung epithelial cells.

Main Methods: sEVs from M(LPS) THP-1 macrophage-like cells after PBDE-47 treatment (sEVs) were characterized by nanoparticle tracking analysis and their microRNA cargo studied by qPCR. Confocal microscopy was applied to study sEVs cellular uptake by A549 cells. The expression of tight junctions (TJs), adhesion molecules, inflammation markers and mucus production in A549 cultured in air liquid interface (ALI) conditions were studied by Real Time PCR and confocal microscopy.

Key Findings: sEVs microRNA cargo analysis showed that the PBDE-47 modulated the expression of the miR-15a-5p, miR29a-3p, miR-143-3p and miR-122-5p. Furthermore, ALI cultured A549 cells incubated with sEVs showed that zonula occludens-1 (p ≤ 0.04), claudin (p ≤ 0.02), E-cadherin (p ≤ 0.006) and Vimentin (p ≤ 0.0008) mRNAs were increased in A549 cells after sEVs treatment. Indeed, Interleukin (IL)-8 (p ≤ 0.008) and mucin (MUC5AC and MUC5B) (p ≤ 0.03 and p ≤ 0.0001) mRNA expression were up- and down-regulated, respectively.

Significance: PBDE-47 treated macrophages secrete sEVs with altered microRNA cargo that affect the mRNA expression of TJs, adhesion molecules, cytokines and EMT markers damaging the normal function of the lung epithelium, potentially contributing to the development of lung diseases.

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Source
http://dx.doi.org/10.1016/j.lfs.2023.121616DOI Listing

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