title: Mucin secretion induced by titanium dioxide nanoparticles.
abstract: Nanoparticle (NP) exposure has been closely associated with the exacerbation and pathophysiology of many respiratory diseases such as Chronic Obstructive Pulmonary Disease (COPD) and asthma. Mucus hypersecretion and accumulation in the airway are major clinical manifestations commonly found in these diseases. Among a broad spectrum of NPs, titanium dioxide (TiO(2)), one of the PM10 components, is widely utilized in the nanoindustry for manufacturing and processing of various commercial products. Although TiO(2) NPs have been shown to induce cellular nanotoxicity and emphysema-like symptoms, whether TiO(2) NPs can directly induce mucus secretion from airway cells is currently unknown. Herein, we showed that TiO(2) NPs (<75 nm) can directly stimulate mucin secretion from human bronchial ChaGo-K1 epithelial cells via a Ca(2+) signaling mediated pathway. The amount of mucin secreted was quantified with enzyme-linked lectin assay (ELLA). The corresponding changes in cytosolic Ca(2+) concentration were monitored with Rhod-2, a fluorescent Ca(2+) dye. We found that TiO(2) NP-evoked mucin secretion was a function of increasing intracellular Ca(2+) concentration resulting from an extracellular Ca(2+) influx via membrane Ca(2+) channels and cytosolic ER Ca(2+) release. The calcium-induced calcium release (CICR) mechanism played a major role in further amplifying the intracellular Ca(2+) signal and in sustaining a cytosolic Ca(2+) increase. This study provides a potential mechanistic link between airborne NPs and the pathoetiology of pulmonary diseases involving mucus hypersecretion.
authors.affiliation: Bioengineering, University of California Merced, Merced, California, United States of America.
authors.forename: Eric Y T
authors.initials: EY
authors.lastname: Chen
authors.forename: Maria
authors.initials: M
authors.lastname: Garnica
authors.forename: Yung-Chen
authors.initials: YC
authors.lastname: Wang
authors.forename: Chi-Shuo
authors.initials: CS
authors.lastname: Chen
authors.forename: Wei-Chun
authors.initials: WC
authors.lastname: Chin
mesh_terms: D002118:Calcium / Q000032:analysis / Q000378:metabolism; D020013:Calcium Signaling; D002460:Cell Line; D004781:Environmental Exposure / Q000009:adverse effects; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D053768:Metal Nanoparticles / Q000633:toxicity*; D009077:Mucins / Q000378:metabolism*; D052638:Particulate Matter / Q000633:toxicity; D014025:Titanium / Q000633:toxicity*
chemical_list: D009077:Mucins; D052638:Particulate Matter; C009495:titanium dioxide; D014025:Titanium; D002118:Calcium