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Disruption of iron homeostasis in mesothelial cells following talc pleurodesis
Citation:
GHIO, A. J., J. M. SOUKUP, L. A. DAILEY, J. Richards, J. TURI, E. N. Pavlisko, AND V. Roggli. Disruption of iron homeostasis in mesothelial cells following talc pleurodesis. AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY. American Thoracic Society, New York, NY, 46(1):80-86, (2012).
Impact/Purpose:
This investigation reports that therapeutic use of talc is dependent on biological effects common to all particles. It disrupts iron homeostasis, generates an oxidative stress, and initiates a biological effect.
Description:
The mechanism for biological effect following particle exposure is incompletely understood. One postulate proposed to explain biological effect after particles is an altered iron homeostasis in the host. The fibro-inflammatory properties of particles are exploited therapeutically with the instillation of massive quantities of talc into the pleural space to provide sclerosis. We tested the postulate that 1) in vitro talc exposure induces a) a disruption in iron homeostasis, b) an oxidative stress and c) a biological effect and 2) talc pleurodesis in humans alters iron homeostasis. In vitro exposures of mesothelial and airway epithelial cells to l00ug/mL talc significantly increased iron import and cell concentrations of the storage protein ferritin. Using dichlorodihydrofluorescein, talc exposure was associated with a time-and concentration-dependent oxidant generation in both cell types. Expression of pro-inflammatory mediators was also increased following in vitro exposures of mesothelial and airway epithelial cells to talc. Relative to pleural tissue collected during pneumonectomy for lung cancer, that from patients having following sclerodesis demonstrated an accumulation of iron and increased expression of iron-related proteins including ferritin, the importer DMTl, and the exporter FPNI. Talc was also observed to translocate to the parenchyma and changes in iron homeostasis were focally distributed to sites of particle retention in the lung. We conclude that talc exposure disrupts iron homeostasis, is associated with an oxidative stress, and results in biological effect (i.e. a fibro-inflammatory response). Talc pleurodesis can function as a model of the human response to a particle exposure, albeit a massive one.
