title: Protection against ozone-induced pulmonary inflammation and cell death by endotoxin pretreatment in mice: role of HO-1.
abstract: Ozone is a ubiquitous air pollutant that can cause acute pulmonary inflammation and cell injury and may contribute to the exacerbation of chronic pulmonary diseases. The molecular mechanisms of ozone-induced cell injury, as well as protective mechanisms against ozone-injury, are not well understood. Since ozone is a reactive oxidant, and heme oxygenase-1 (HO-1) is an antioxidant enzyme induced by many oxidative stimuli, we hypothesized that HO-1 is one of the protective mechanisms against ozone-induced cell injury, as well as pulmonary inflammation. In the current study, C57Bl/6 mice were pretreated with a low level of endotoxin (lipopolysaccharide, LPS) (0.5 mg/kg) to induce HO-1, and 16 h later were exposed to 1 ppm ozone for 3 h. Endotoxin pretreatment caused a significant protection against ozone-induced pulmonary inflammation and cell injury in bronchoalveolar lavage (BAL) cells. The protection by endotoxin pretreatment against ozone-induced inflammation and necrosis in BAL cells was abolished by the cotreatment with a heme oxygenase inhibitor, tin protoporphyrin IX dichloride (SnPP), suggesting that HO-1 is responsible for the protection against ozone-induced pulmonary inflammation and BAL cell necrosis. Therefore, since HO-1 is induced following ozone exposure, HO-1 may contribute to the development of cellular adaptation to chronic ozone exposure.
authors.affiliation: Department of Internal Medicine, Toxicology Program, University of Texas Houston Medical School, Houston, Texas, USA.
authors.forename: L
authors.initials: L
authors.lastname: Li
authors.forename: R F
authors.initials: RF
authors.lastname: Hamilton
authors.forename: A
authors.initials: A
authors.lastname: Holian
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D002470:Cell Survival / Q000187:drug effects; D006419:Heme Oxygenase (Decyclizing) / Q000502:physiology*; D051547:Heme Oxygenase-1; D007249:Inflammation / Q000139:chemically induced*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008168:Lung / Q000187:drug effects* / Q000473:pathology; D008297:Male; D008565:Membrane Proteins; D051379:Mice; D008810:Mice, Inbred C57BL; D010126:Ozone / Q000633:toxicity*
chemical_list: D008070:Lipopolysaccharides; D008565:Membrane Proteins; D010126:Ozone; D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1; C496542:Hmox1 protein, mouse