Assessing the NLRP3 Inflammasome Activating Potential of a Large Panel of Micro- and Nanoplastics in THP-1 Cells.
Mathias BuschGerrit BredeckFriedrich WaagKhosrow RahimiHaribaskar RamachandranTobias BesselStephan BarcikowskiAndreas HerrmannAndrea RossiRoel P F SchinsPublished in: Biomolecules (2022)
Due to the ubiquity of environmental micro- and nanoplastics (MNPs), inhalation and ingestion by humans is very likely, but human health effects remain largely unknown. The NLRP3 inflammasome is a key player of the innate immune system and is involved in responses towards foreign particulate matter and the development of chronic intestinal and respiratory inflammatory diseases. We established NLRP3 -proficient and -deficient THP-1 cells as an alternative in vitro screening tool to assess the potential of MNPs to activate the NLRP3 inflammasome. By investigating cytokine release (IL-1β and IL-8) and cytotoxicity after treatment with engineered nanomaterials, this in vitro approach was compared to earlier published ex vivo murine bone marrow-derived macrophages and in vivo data. This approach showed a strong correlation with previously published data, verifying that THP-1 cells are a suitable model to investigate NLRP3 inflammasome activation. We then investigated the proinflammatory potential of eight MNPs of different size, shape, and chemical composition. Only amine-modified polystyrene (PS-NH 2 ) acted as a direct NLRP3 activator. However, polyethylene terephthalate (PET), polyacrylonitrile (PAN), and nylon (PA6) induced a significant increase in IL-8 release in NLRP3 -/- cells. Our results suggest that most MNPs are not direct activators of the NLRP3 inflammasome, but specific MNP types might still possess pro-inflammatory potential via other pathways.
Keyphrases
- nlrp inflammasome
- induced apoptosis
- cell cycle arrest
- particulate matter
- immune response
- oxidative stress
- signaling pathway
- cell death
- computed tomography
- mesenchymal stem cells
- bone marrow
- mass spectrometry
- inflammatory response
- pi k akt
- drug induced
- single molecule
- artificial intelligence
- diabetic rats
- atomic force microscopy