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 (TiO2), one of the PM10 components, is widely utilized in the nanoindustry for manufacturing and processing of various commercial products. Although TiO2 NPs have been shown to induce cellular nanotoxicity and emphysema-like symptoms, whether TiO2 NPs can directly induce mucus secretion from airway cells is currently unknown. Herein, we showed that TiO2 NPs (<75 nm) can directly stimulate mucin secretion from human bronchial ChaGo-K1 epithelial cells via a Ca2+ signaling mediated pathway. The amount of mucin secreted was quantified with enzyme-linked lectin assay (ELLA). The corresponding changes in cytosolic Ca2+ concentration were monitored with Rhod-2, a fluorescent Ca2+ dye. We found that TiO2 NP-evoked mucin secretion was a function of increasing intracellular Ca2+ concentration resulting from an extracellular Ca2+ influx via membrane Ca2+ channels and cytosolic ER Ca2+ release. The calcium-induced calcium release (CICR) mechanism played a major role in further amplifying the intracellular Ca2+ signal and in sustaining a cytosolic Ca2+ increase. This study provides a potential mechanistic link between airborne NPs and the pathoetiology of pulmonary diseases involving mucus hypersecretion.

A mixture of anatase and rutile TiO2 nanoparticles induces histamine secretion in mast cells

“…The question of whether TiO 2 NPs can trigger a similar process is unclear. Our experiments confirmed that [Ca 2+ ] C failed to increase significantly when cells were treated with TiO 2 NPs in Ca 2+ -free Hanks' solution (Figure 2B) or blocked with CdCl 2 (a general Ca 2+ channel blocker) (Figure 2C) [17]. We then demonstrated that TiO 2 NPs can activate L-type voltage-gated Ca 2+ channels on mast cells, allowing extracellular Ca 2+ influx into the cytosol (Figure 2D and 2E).…”

Citrullination of Proteins: A Common Post-Translational Modification Pathway Induced by Different Nanoparticles In Vitro and In Vivo

“…We observed increased intracellular Ca 2+ in the cells exposed to SiO 2 NPs, SWCNTs and ufCB. Nanomaterials have been shown to accelerate extracellular Ca 2+ influx via compromised cell membrane integrity [68-70]. Nanosized titanium dioxide has been shown to increase levels of cytosolic Ca 2+ in human bronchial ChaGo-K1 epithelial cells [68].…”

“…Nanomaterials have been shown to accelerate extracellular Ca 2+ influx via compromised cell membrane integrity [68-70]. Nanosized titanium dioxide has been shown to increase levels of cytosolic Ca 2+ in human bronchial ChaGo-K1 epithelial cells [68]. To explore if nanomaterials mediated Ca 2+ influx led to PAD-dependent protein citrullination, human epithelial A549 and phagocytic THP-1 cells were exposed to SWCNTs, ufCB and SiO 2 NPs in the presence of a Ca 2+ channel blocker.…”

Intracellular Signal Modulation by Nanomaterials

“…A sustained elevation of Ca 2+ was achieved by inducing the release of Ca 2+ from the endoplasmic reticulum leading to histamine secretion. TiO 2 NPs also stimulate mucin secretion in epithelial cells by inducing extracellular Ca 2+ influx and calcium release from the endoplasmic reticulum (Chen et al, 2011). Intracellular Ca 2+ increase is also involved in the inhibition of cell proliferation by Ag NPs (Asharani et al, 2009).…”