6533b870fe1ef96bd12cf2d0
RESEARCH PRODUCT
Beclomethasone dipropionate and formoterol reduce oxidative/nitrosative stress generated by cigarette smoke extracts and IL-17A in human bronchial epithelial cells.
Angela Marina MontalbanoGiulia AnzaloneGiulia AnzaloneAnna BonannoEleonora IngrassiaGiusy Daniela AlbanoGiusy Daniela AlbanoGabriele NicoliniRosalia GagliardoLoredana RiccobonoMark GjomarkajCaterina Di SanoMirella Profitasubject
Transcription GeneticNitric Oxide Synthase Type IIBronchiOxidative phosphorylationPharmacologyGene Expression Regulation EnzymologicCell Linechemistry.chemical_compoundFormoterol FumarateSmokeNitrilesmedicineButadienesGene silencingHumansGene SilencingPromoter Regions GeneticPharmacologychemistry.chemical_classificationReactive oxygen speciesbiologyNitrotyrosineInterleukin-17BeclomethasoneEpithelial CellsTobacco ProductsReactive Nitrogen SpeciesNitric oxide synthaseOxidative StressSTAT1 Transcription FactorchemistryEthanolaminesImmunologySTAT proteinbiology.proteinPhosphorylationFormoterolBiomarkersmedicine.drugdescription
Interleukin-17A (IL-17A), cigarette smoke and oxidative/nitrosative stress are involved in inflammatory airway diseases, and the mechanisms behind these processes are still poorly understood. We investigated whether recombinant human IL-17A (rhIL-17A), in combination with cigarette smoke extracts (CSE), increases the levels of inducibile nitric oxide synthase (iNOS), reactive oxygen species, nitrotyrosine (NT) and the activation of signal transducer and activator of transcription 1 (STAT-1) in normal human bronchial epithelial cells (16HBE). The effect of beclomethasone dipropionate (BDP), formoterol and their combination was also evaluated. We demonstrated that rhIL-17A or CSE alone increases iNOS expression, reactive oxygen species and NT production and STAT-1 downstream signalling activation in terms of STAT-1ser727 and STAT-1tyr701 phosphorylation. The combination of both stimuli further increased iNOS, ROS, NT and STAT-1ser727 phosphorylation. The silencing of STAT-1 expression partially reduced the levels of iNOS, reactive oxygen species and NT generated by rhIL-17A and inhibited the effect of CSE alone in 16HBE cells. The treatment of the cells with the MEK1/2 inhibitor U0126 (1,4-diamino-2,3-dicyano-1,4-bis (o-aminophenylmercapto butadiene) abolished the expression of iNOS and STAT-1ser727 phosphorylation generated by rhIL-17A. 16HBE treated with BDP or formoterol alone partially suppressed the effect of IL-17A or CSE on ROS, NT, and STAT-1 activation. Furthermore the use of the drugs in combination showed an additive effect in 16HBE. Our findings demonstrate that IL-17A increases oxidative/nitrosative markers, likely via ERK1/2 downstream signalling and STAT-1 pathway activation in human bronchial epithelial cells. BDP and formoterol treatment reduces this effect showing an additive effect used in combination.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2013-06-15 | European journal of pharmacology |