title: Silver nanoparticles induce anti-proliferative effects on airway smooth muscle cells. Role of nitric oxide and muscarinic receptor signaling pathway.
abstract: Silver nanoparticles (AgNPs) are used to manufacture materials with new properties and functions. However, little is known about their toxic or beneficial effects on human health, especially in the respiratory system, where its smooth muscle (ASM) regulates the airway contractility by different mediators, such as acetylcholine (ACh) and nitric oxide (NO). The aim of this study was to evaluate the effects of AgNPs on ASM cells. Exposure to AgNPs induced ACh-independent expression of the inducible nitric oxide synthase (iNOS) at 100 μg/mL, associated with excessive production of NO. AgNPs induced the muscarinic receptor activation, since its blockage with atropine and blockage of its downstream signaling pathway inhibited the NO production. AgNPs at 10 and 100 μg/mL induced ACh-independent prolonged cytotoxicity and decreased cellular proliferation mediated by the muscarinic receptor-iNOS pathway. However, the concentration of 100 μg/mL of AgNPs induced muscarinic receptor-independent apoptosis, suggesting the activation of multiple pathways. These data indicate that AgNPs induce prolonged cytotoxic and anti-proliferative effects on ASM cells, suggesting an activation of the muscarinic receptor-iNOS pathway. Further investigation is required to understand the full mechanisms of action of AgNPs on ASM under specific biological conditions.
authors.affiliation: Universidad Autónoma de San Luis Potosí, Facultad de Ciencias Químicas, San Luis Potosí, Mexico.
authors.forename: Manuel A
authors.initials: MA
authors.lastname: Ramírez-Lee
authors.forename: Héctor
authors.initials: H
authors.lastname: Rosas-Hernández
authors.forename: Samuel
authors.initials: S
authors.lastname: Salazar-García
authors.forename: José Manuel
authors.initials: JM
authors.lastname: Gutiérrez-Hernández
authors.forename: Ricardo
authors.initials: R
authors.lastname: Espinosa-Tanguma
authors.forename: Francisco J
authors.initials: FJ
authors.lastname: González
authors.forename: Syed F
authors.initials: SF
authors.lastname: Ali
authors.forename: Carmen
authors.initials: C
authors.lastname: González
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects*; D008297:Male; D053768:Metal Nanoparticles / Q000633:toxicity*; D032389:Myocytes, Smooth Muscle / Q000166:cytology / Q000187:drug effects*; D009569:Nitric Oxide / Q000502:physiology*; D052247:Nitric Oxide Synthase Type II / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D011976:Receptors, Muscarinic / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*; D012834:Silver; D014132:Trachea / Q000187:drug effects* / Q000473:pathology
chemical_list: D011976:Receptors, Muscarinic; D009569:Nitric Oxide; D012834:Silver; D052247:Nitric Oxide Synthase Type II; D000109:Acetylcholine
keywords: Airway; Apoptosis; Muscarinic receptor; Nitric oxide; Proliferation; Silver nanoparticles