TY - JOUR
T1 - Protection against ozone-induced pulmonary inflammation and cell death by endotoxin pretreatment in mice
T2 - Role of HO-1
AU - Li, L.
AU - Hamilton, Jr
AU - Holian, A.
N1 - Funding Information:
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]
PY - 2000
Y1 - 2000
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=0033658765&partnerID=8YFLogxK
U2 - 10.1080/08958370050198557
DO - 10.1080/08958370050198557
M3 - Article
C2 - 11203434
AN - SCOPUS:0033658765
SN - 0895-8378
VL - 12
SP - 1225
EP - 1238
JO - Inhalation Toxicology
JF - Inhalation Toxicology
IS - 12
ER -