Compounds collected from indium-tin oxide production induce inflammatory responses from cultured macrophages and bronchial epithelial cells.
Badding-MA; Schwegler-Berry-D; Cummings-KJ; Leonard-SS
Toxicologist 2014 Mar; 138(1):320
Indium-tin oxide (ITO) is used to make transparent conductive coatings for touch-screen and liquid crystal display electronics. Lung disease among workers in the ITO industry is an emerging occupational health concern as the demand for consumer electronics continues to increase. Epidemiologic studies have shown indium compound-exposed workers to have pulmonary alveolar proteinosis and fibrotic interstitial lung disease. However, the molecular mechanisms behind indium compounds' toxicity remain largely unknown. Thus, we aim to uncover how compounds encountered during ITO production affect cultured cells and ultimately, contribute to the pathogenesis of indium lung disease. We hypothesize that indium compounds (8 different samples collected from various stages at an ITO facility) cause lung pathology through direct cytotoxicity and/or via inflammatory signaling from exposed cells. Preliminary studies showed that exposure of RAW 264.7 monocyte macrophages and BEAS-2B bronchial epithelial cells to indium compounds resulted in significantly reduced viability. Microscopy techniques revealed that various indium compounds interact with and are engulfed by both cell lines within 1 to 3 hours, suggesting that cellular reactions may be occurring very rapidly. Indeed, nuclear factor kappa beta (NFkappaB) activation occurs within 3 hours of treatment with compounds containing sintered ITO in both cell lines. Robust cytokine production (TNFalpha, IL-1beta, IL-6, and IL-8) following cellular exposures confirmed that pro-inflammatory responses are indeed occurring. Our results suggest that inflammatory responses to indium compounds by both pulmonary macrophages and epithelial cells may initiate and propagate indium lung disease. These findings have provided a better understanding of the molecular mechanisms behind an emerging occupational health issue and will aid in the discovery of biomarkers for disease prevention.
Toxicology; Air-quality; Biological-factors; Respiration; Respiratory-irritants; Respiratory-system-disorders; Pulmonary-system; Pulmonary-system-disorders; Pulmonary-function; Exposure-levels; Laboratory-animals; Animals; Electronic-components; Electronic-equipment; Epidemiology; Indium-compounds
The Toxicologist. Society of Toxicology 53rd Annual Meeting and ToxExpo, March 23-27, 2014, Phonex, Arizona