title: Human eosinophils are direct targets to nanoparticles: Zinc oxide nanoparticles (ZnO) delay apoptosis and increase the production of the pro-inflammatory cytokines IL-1β and IL-8.
abstract: Zinc oxide NPs (ZnO) have been recently proposed as novel candidates for the treatment of allergic inflammatory diseases. Paradoxically, recent data suggested that ZnO could cause eosinophilic airway inflammation in rodents. Despite the above observations, there are currently no studies reporting direct interaction between a given NP and human eosinophils themselves. In this study, freshly isolated human eosinophils were incubated with ZnO and several cellular functions were studied. We found that ZnO delay human eosinophil apoptosis, partially by inhibiting caspases and by preventing caspase-4 and Bcl-xL degradation. ZnO do not induce production of reactive oxygen species but increase de novo protein synthesis. In addition, ZnO were found to increase the production of the proinflammatory IL-1β and IL-8 cytokines. Using a pharmacological approach, we demonstrated that inhibition of caspase-1 reversed the ability of ZnO to induce IL-1β and IL-8 production, whereas inhibition of caspase-4 only reversed that of IL-8. Our results indicate the necessity of conducting studies to determine the potential of using NP as nanotherapies, particularly in diseases in which eosinophils may be involved. We conclude that, indeed, human eosinophils represent potential new direct targets to NPs, ZnO in the present case.
authors.affiliation: Laboratoire de recherche en inflammation et physiologie des granulocytes, Université du Québec, INRS-Institut Armand-Frappier, Laval, Québec, Canada.
authors.forename: Luis Rafael
authors.initials: LR
authors.lastname: Silva
authors.affiliation: Laboratoire de recherche en inflammation et physiologie des granulocytes, Université du Québec, INRS-Institut Armand-Frappier, Laval, Québec, Canada. Electronic address: denis.girard@iaf.inrs.ca.
authors.forename: Denis
authors.initials: D
authors.lastname: Girard
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D061945:Caspase Inhibitors / Q000494:pharmacology; D020169:Caspases / Q000235:genetics / Q000378:metabolism; D048430:Cell Shape / Q000187:drug effects; D002470:Cell Survival; D004804:Eosinophils / Q000187:drug effects* / Q000502:physiology; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D053583:Interleukin-1beta / Q000235:genetics / Q000378:metabolism*; D016209:Interleukin-8 / Q000235:genetics / Q000378:metabolism*; D053768:Metal Nanoparticles / Q000737:chemistry*; D015034:Zinc Oxide / Q000737:chemistry / Q000494:pharmacology*; D051020:bcl-X Protein / Q000235:genetics / Q000378:metabolism
chemical_list: C494811:BCL2L1 protein, human; D061945:Caspase Inhibitors; D053583:Interleukin-1beta; D016209:Interleukin-8; D051020:bcl-X Protein; D020169:Caspases; D015034:Zinc Oxide
keywords: Apoptosis; Caspases; Cytokines; De novo protein synthesis; Eosinophils; Nanoparticles