Abstract
BackgroundNowadays, effects of fine particulate matter (PM2.5) are well-documented and related to oxidative stress and pro-inflammatory response. Nevertheless, epidemiological studies show that PM2.5 exposure is correlated with an increase of pulmonary cancers and the remodeling of the airway epithelium involving the regulation of cell death processes. Here, we investigated the components of Parisian PM2.5 involved in either the induction or the inhibition of cell death quantified by different parameters of apoptosis and delineated the mechanism underlying this effect.ResultsIn this study, we showed that low levels of Parisian PM2.5 are not cytotoxic for three different cell lines and primary cultures of human bronchial epithelial cells. Conversely, a 4 hour-pretreatment with PM2.5 prevent mitochondria-driven apoptosis triggered by broad spectrum inducers (A23187, staurosporine and oligomycin) by reducing the mitochondrial transmembrane potential loss, the subsequent ROS production, phosphatidylserine externalization, plasma membrane permeabilization and typical morphological outcomes (cell size decrease, massive chromatin and nuclear condensation, formation of apoptotic bodies). The use of recombinant EGF and specific inhibitor led us to rule out the involvement of the classical EGFR signaling pathway as well as the proinflammatory cytokines secretion. Experiments performed with different compounds of PM2.5 suggest that endotoxins as well as carbon black do not participate to the antiapoptotic effect of PM2.5. Instead, the water-soluble fraction, washed particles and organic compounds such as polycyclic aromatic hydrocarbons (PAH) could mimic this antiapoptotic activity. Finally, the activation or silencing of the aryl hydrocarbon receptor (AhR) showed that it is involved into the molecular mechanism of the antiapoptotic effect of PM2.5 at the mitochondrial checkpoint of apoptosis.ConclusionsThe PM2.5-antiapoptotic effect in addition to the well-documented inflammatory response might explain the maintenance of a prolonged inflammation state induced after pollution exposure and might delay repair processes of injured tissues.
Highlights
Nowadays, effects of fine particulate matter (PM2.5) are well-documented and related to oxidative stress and pro-inflammatory response
Recent data demonstrate that short exposure of bronchial or nasal epithelial cells to urban PM2.5 provokes the secretion of epidermal growth factor receptor (EGFR) ligands and Amphiregulin, which leads to granulocyte monocyte colony-stimulating factor (GM-CSF) secretion via an autocrine pathway [9]
In order to determine if this lack of toxicity is specific to 16HBE cells, we extended our study to other human bronchial epithelial cells, such as NCI-H292 and BEAS-2B cell lines and to non-differentiated primary human bronchial epithelial cells (NHBE)
Summary
Effects of fine particulate matter (PM2.5) are well-documented and related to oxidative stress and pro-inflammatory response. Epidemiological studies show that PM2.5 exposure is correlated with an increase of pulmonary cancers and the remodeling of the airway epithelium involving the regulation of cell death processes. In vitro short-term exposure to PM is associated with an inflammatory response as a consequence of cellular oxidative stress increase [3]. Chronic exposure was associated with persistence of particles into the lungs leading to bronchioli wall thickening [15] and airway remodeling characterized by epithelial mucus-producing cells metaplasia, subepithelial fibrosis and airway smooth muscle hypertrophy/hyperplasia as observed in chronic asthma and COPD [16]. Mechanisms involved in airway remodelling might be the excessive cell proliferation as well as the resistance to the apoptotic cell death
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