Apoptosis and Bax expression are increased by coal dust in the polycyclic aromatic hydrocarbon-exposed lung.
BACKGROUND
Miners inhaling respirable coal dust (CD) frequently develop coal workers' pneumoconiosis, a dust-associated pneumoconiosis characterized by lung inflammation and variable fibrosis. Many coal miners are also exposed to polycyclic aromatic hydrocarbon (PAH) components of diesel engine exhaust and cigarette smoke, which may contribute to lung disease in these workers. Recently, apoptosis was reported to play a critical role in the development of another pneumoconiosis of miners, silicosis. In addition, CD was reported to suppress cytochrome P450 1A1 (CYP1A1) induction by PAHs.


METHODS
We investigated the hypothesis that apoptosis plays a critical role in lung injury and down-regulation of CYP1A1 induction in mixed exposures to CD and PAHs. We exposed rats intratracheally to 0.0, 2.5, 10.0, 20.0, or 40.0 mg/rat CD and, 11 days later, to intraperitoneal beta-naphthoflavone (BNF) , a PAH. In another group of rats exposed to CD and BNF, caspase activity was inhibited by injection of the pan-caspase inhibitor Q-VD-OPH [quinoline-Val-Asp (OMe) -CH2-OPH].


RESULTS
In rats exposed to BNF, CD exposure increased alveolar expression of the proapoptotic mediator Bax but decreased CYP1A1 induction relative to BNF exposure alone. Pan-caspase inhibition decreased CD-associated Bax expression and apoptosis but did not restore CYP1A1 activity. Further, CD-induced lung inflammation and alveolar epithelial cell hypertrophy and hyperplasia were not suppressed by caspase inhibition.


CONCLUSIONS
Combined BNF and CD exposure increased Bax expression and apoptosis in the lung, but Bax and apoptosis were not the major determinants of early lung injury in this model.
Ghanem
Mohamed M
MM
Genetics and Developmental Biology Program, West Virginia University, Morgantown, West Virginia, USA.
Battelli
Lori A
LA
Mercer
Robert R
RR
Scabilloni
James F
JF
Kashon
Michael L
ML
Ma
Jane Y C
JY
Nath
Joginder
J
Hubbs
Ann F
AF
D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D001189:Aryl Hydrocarbon Hydroxylases / Q000378:metabolism; D061945:Caspase Inhibitors; D020169:Caspases / Q000378:metabolism; D003031:Coal / Q000633:toxicity*; D019363:Cytochrome P-450 CYP1A1 / Q000378:metabolism*; D065633:Cytochrome P-450 CYP1B1; D004305:Dose-Response Relationship, Drug; D004391:Dust; D005786:Gene Expression Regulation / Q000187:drug effects*; D008168:Lung / Q000187:drug effects* / Q000473:pathology; D008297:Male; D011014:Pneumonia / Q000139:chemically induced; D011084:Polycyclic Aromatic Hydrocarbons / Q000633:toxicity*; D011650:Pulmonary Alveoli / Q000166:cytology / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D019324:beta-Naphthoflavone / Q000633:toxicity
D061945:Caspase Inhibitors; D003031:Coal; D004391:Dust; D011084:Polycyclic Aromatic Hydrocarbons; D019324:beta-Naphthoflavone; D001189:Aryl Hydrocarbon Hydroxylases; C585499:Cyp1b1 protein, rat; D019363:Cytochrome P-450 CYP1A1; D065633:Cytochrome P-450 CYP1B1; D020169:Caspases