title: Human peripheral blood mononuclear cells (PBMCs) from smokers release higher levels of IL-1-like cytokines after exposure to combustion-generated ultrafine particles.
abstract: Ultrafine particles (UFP) generated by combustion processes are often associated with adverse health effects. However, little is known about the inflammatory processes generated by UFP that may underlie their toxicological activity. Murine macrophages (J774.1 cells) and human peripheral blood mononuclear cells (PBMCs) were used to evaluate the molecular mechanism underlying the pro-inflammatory activity of UFP. The addition of soot particles to J774.1 cells induced a concentration-dependent release of IL-1α, IL-1β and IL-33 This effect was not associated with cell death and, in contrast to literature, was pronounced at very low concentrations (5-100 pg/ml). Similarly, UFP induced the release of IL-1α, IL-18 and IL-33 by PBMCs. However, this effect was solely observed in PBMCs obtained from smokers, as the PBMCs from non-smokers instead released higher levels of IL-10. The release of these cytokines after UFP exposure was caspase-1- and NLRP3 inflammasome-dependent in PBMCs from healthy smokers, whereas IL-1α release was calpain-dependent. These results show that UFP at very low concentrations are able to give rise to an inflammatory process that is responsible for IL-1α, IL-18 and IL-33 release, which is pronounced in PBMCs from smokers, confirming that these individuals are especially susceptible to inflammatory-based airway diseases once exposed to air pollution.
authors.affiliation: Dipartimento di Ingegneria Chimica, dei Materiali e della Produzione Industriale, Università degli Studi di Napoli Federico II, Piazzale V. Tecchio, 80, Napoli, Italy.|Istituto di Ricerche sulla Combustione - National Research Center (CNR), Piazzale V. Tecchio, 80, Napoli, Italy.
authors.forename: Gianluigi
authors.initials: G
authors.lastname: De Falco
authors.affiliation: Department of Pharmacy (DIFARMA), University of Salerno; ImmunePharma s.r.l., Via Giovanni Paolo II 132, Salerno, Italy.
authors.forename: Michela
authors.initials: M
authors.lastname: Terlizzi
authors.affiliation: Dipartimento di Ingegneria Chimica, dei Materiali e della Produzione Industriale, Università degli Studi di Napoli Federico II, Piazzale V. Tecchio, 80, Napoli, Italy.
authors.forename: Mariano
authors.initials: M
authors.lastname: Sirignano
authors.affiliation: Istituto di Ricerche sulla Combustione - National Research Center (CNR), Piazzale V. Tecchio, 80, Napoli, Italy.
authors.forename: Mario
authors.initials: M
authors.lastname: Commodo
authors.affiliation: Dipartimento di Ingegneria Chimica, dei Materiali e della Produzione Industriale, Università degli Studi di Napoli Federico II, Piazzale V. Tecchio, 80, Napoli, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: D'Anna
authors.affiliation: Department of Pharmacy (DIFARMA), University of Salerno; ImmunePharma s.r.l., Via Giovanni Paolo II 132, Salerno, Italy.
authors.forename: Rita P
authors.initials: RP
authors.lastname: Aquino
authors.affiliation: Department of Pharmacy (DIFARMA), University of Salerno; ImmunePharma s.r.l., Via Giovanni Paolo II 132, Salerno, Italy.
authors.forename: Aldo
authors.initials: A
authors.lastname: Pinto
authors.affiliation: Department of Pharmacy (DIFARMA), University of Salerno; ImmunePharma s.r.l., Via Giovanni Paolo II 132, Salerno, Italy.
authors.forename: Rosalinda
authors.initials: R
authors.lastname: Sorrentino
mesh_terms: D000818:Animals; D020170:Caspase 1 / Q000378:metabolism; D002478:Cells, Cultured; D006801:Humans; D053582:Interleukin-1alpha / Q000378:metabolism*; D053583:Interleukin-1beta / Q000378:metabolism*; D000067596:Interleukin-33 / Q000378:metabolism*; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008264:Macrophages / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein / Q000378:metabolism; D010316:Particle Size; D000074285:Smokers; D053260:Soot / Q000737:chemistry / Q000633:toxicity*
chemical_list: D053582:Interleukin-1alpha; D053583:Interleukin-1beta; D000067596:Interleukin-33; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C453881:NLRP3 protein, human; D053260:Soot; D020170:Caspase 1