Polycyclic aromatic hydrocarbon components contribute to the mitochondria-antiapoptotic effect of fine particulate matter on human bronchial epithelial cells via the aryl hydrocarbon receptor.
BACKGROUND
Nowadays, 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.


RESULTS
In 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.


CONCLUSIONS
The 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.
Ferecatu
Ioana
I
Université Paris Diderot-Paris 7, Unit of Functional and Adaptive Biology (BFA) CNRS EAC 4413, Laboratory of Molecular and Cellular Responses to Xenobiotics, Bâtiment Buffon, case courrier 7073, 5 rue Thomas Mann, 75013 Paris, France.
Borot
Marie-Caroline
MC
Bossard
Camille
C
Leroux
Melanie
M
Boggetto
Nicole
N
Marano
Francelyne
F
Baeza-Squiban
Armelle
A
Andreau
Karine
K
D000393:Air Pollutants / Q000737:chemistry / Q000633:toxicity*; D066258:Amphiregulin; D017209:Apoptosis / Q000187:drug effects*; D001980:Bronchi / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D000001:Calcimycin / Q000494:pharmacology; D002460:Cell Line; D002463:Cell Membrane Permeability / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D066255:EGF Family of Proteins; D004848:Epithelium / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D006023:Glycoproteins / Q000378:metabolism; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D009840:Oligomycins / Q000494:pharmacology; D010316:Particle Size; D052638:Particulate Matter / Q000737:chemistry / Q000633:toxicity*; D011084:Polycyclic Aromatic Hydrocarbons / Q000737:chemistry / Q000633:toxicity*; D017382:Reactive Oxygen Species; D019311:Staurosporine / Q000494:pharmacology
C587848:AREG protein, human; D000393:Air Pollutants; D066258:Amphiregulin; D066255:EGF Family of Proteins; D006023:Glycoproteins; D036341:Intercellular Signaling Peptides and Proteins; D009840:Oligomycins; D052638:Particulate Matter; D011084:Polycyclic Aromatic Hydrocarbons; D017382:Reactive Oxygen Species; D000001:Calcimycin; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D019311:Staurosporine