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, C57BI/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.
| Original language | English |
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| Pages (from-to) | 1225-1238 |
| Number of pages | 14 |
| Journal | Inhalation Toxicology |
| Volume | 12 |
| Issue number | 12 |
| DOIs | |
| State | Published - 2000 |
Funding
Received 4 February 2000; sent for revision 12 April 2000; revision received 2 June 2000; accepted 9 June 2000. This work was supported in part by National Institutes of Health grant ES08752. Address correspondence to Andrij Holian, PhD, at his current address: Center for Environmental Health Sciences, Department of Pharmaceutical Sciences, University of Montana, 32 Campus Drive #1552, Missoula, MT 59812-1552, USA. E-mail: [email protected]
| Funder number |
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| R01ES008752 |