Marijuana smoking is associated with inflammation, cellular atypia, and molecular dysregulation of the tracheobronchial epithelium. While marijuana smoke shares many components in common with tobacco, it also contains a high concentration of Δ9-tetrahydrocannabinol (THC). The potential contribution of THC to airway injury was assessed by exposing primary cultures of human small airway epithelial (SAE) cells to THC (0.1-10.0 μg/ml) for either 1 day or 7 days. THC induced a time- and concentration-dependent decrease in cell viability, ATP level, and mitochondrial membrane potential. Using a targeted gene expression array, we observed acute changes (24 h) in the expression of mRNA for caspase-8, catalase, Bax, early growth response-1, cytochrome P4501A1 (CYP1A1), metallothionein 1A, PLAB, and heat shock factor 1 (HSF1). After 7 days of exposure, decrease in expression of mRNA for heat shock proteins (HSPs) and the pro-apoptotic protein Bax was observed, while expression of GADD45A, IL-1A, CYP1A1, and PTGS-2 increased significantly. These findings suggest a contribution of THC to DNA damage, inflammation, and alterations in apoptosis. Treatment with selected prototypical toxicants, 2,3,7,8- tetrachlorodibenznzo-p-dioxin (TCDD) and carbonyl cyanide-p-(trifluoramethoxy)- phenyl hydrazone (FCCP), produced partially overlapping gene expression profiles suggesting some similarity in mechanism of action with THC. THC, delivered as a component of marijuana smoke, may induce a profile of gene expression that contributes to the pulmonary pathology associated with marijuana use.
|Titolo:||Immune activation and dental amalgams|
|Parole Chiave:||Airway epithelial cell; cDNA array; Gene expression; Marijuana; Tetrahydrocannabinol|
|Settore Scientifico Disciplinare:||Settore MED/35 - Malattie Cutanee e Veneree|
Settore MED/28 - Malattie Odontostomatologiche
|Data di pubblicazione:||2005|
|Digital Object Identifier (DOI):||10.1016/j.toxlet.2005.03.008|
|Appare nelle tipologie:||01 - Articolo su periodico|