Coarse particulate matter (PM10) induce an inflammatory response through the NLRP3 activation

ABSTRACT: Introduction: PM exposure can induce inflammatory and oxidative responses; however, differences in these adverse effects have been reported depending on the chemical composition and size. Moreover, inflammatory mechanisms such as NLRP3 activation by PM10 have yet to be explored. Objective: To assess the impact of PM10 on cell cytotoxicity and the inflammatory response through in vitro and in vivo models. Methodology: Peripheral blood mononuclear cells (PBMCs) from healthy donors were exposed to PM10. Cytotoxicity was determined using the LDH assay; the expression of inflammasome components and the production of proinflammatory cytokines were quantified through qPCR and ELISA, respectively; and the formation of ASC complexes was examined using confocal microscopy. For in vivo analysis, male C57BL6 mice were intranasally challenged with PM10 and bronchoalveolar lavage fluid was collected to determine cell counts and quantification of proinflammatory cytokines by ELISA. RNA was extracted from lung tissue, and the gene expression of inflammatory mediators was quantified. Results: PM10 exposure induced significant cytotoxicity at concentrations over 100 μg/mL. Moreover, PM10 enhances the gene expression and release of pro-inflammatory cytokines in PBMCs, particularly IL-1β; and induces the formation of ASC complexes in a dose-dependent manner. In vivo, PM10 exposure led to cell recruitment to the lungs, which was characterized by a significant increase in polymorphonuclear cells compared to control animals. Furthermore, PM10 induces the expression of several inflammatory response-related genes, such as NLRP3, IL-1β and IL-18, within lung tissue. Conclusión: Briefly, PM10 exposure reduced the viability of primary cells and triggered an inflammatory response, involving NLRP3 inflammasome activation and the subsequent production of IL-1β. Moreover, PM10 induces the recruitment of cells to the lung and the expression of multiple cytokines; this phenomenon could contribute to epithelial damage and, thus to the development and exacerbation of respiratory diseases such as viral infections.

• Autores: Marín Palma, Leidy Damariz; Tabares Guevara, Jorge Humberto; Taborda Vanegas, Natalia Andrea; Rugeles López, María Teresa; Hernández López, Juan Carlos
• Tipo de recurso: Article of investigation
• Fecha de publicación: 2024
• Institución: Universidad de Antioquia
• Repositorio: Repositorio UdeA
• Idioma: eng
• OAI Identifier: oai:bibliotecadigital.udea.edu.co:10495/41371
• Acceso en línea: https://hdl.handle.net/10495/41371
• Palabra clave: Contaminación del Aire; Air pollution; Inflamación; Inflammation; Inflamasomas; Inflammasomes; Pneumonia; Neumonía; Material Particulado; Particulate Matter; Proteína con Dominio Pirina 3 de la Familia NLR; NLR Family, Pyrin Domain-Containing 3 Protein; https://id.nlm.nih.gov/mesh/D000397; https://id.nlm.nih.gov/mesh/D007249; https://id.nlm.nih.gov/mesh/D058847; https://id.nlm.nih.gov/mesh/D011014; https://id.nlm.nih.gov/mesh/D052638; https://id.nlm.nih.gov/mesh/D000071199
• Rights: openAccess
• License: http://creativecommons.org/licenses/by/2.5/co/