Proliferation of airway epithelium after ozone exposure: effect of apocynin and dexamethasone.
Ozone is an environmental pollutant with potent oxidizing properties. We investigated whether exposure to ozone-induced cell proliferation in the lungs of rats, and determined the effect of an antioxidant and of a glucocorticosteroid in Brown-Norway (BN) rats. Following single ozone exposure (0.5, 1.0, or 3.0 ppm for 6 h), proliferating cell nuclear antigen (PCNA) expression, as determined with immunohistochemistry, was significantly increased in the bronchial epithelium and alveolar epithelium as compared with controls exposed to filtered air with a maximal effect at 24 to 48 h (p < 0.001). Apocynin (5 mg/kg, orally), a reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase inhibitor, reduced the PCNA index in bronchial epithelium induced by ozone (3 ppm, 6 h) from 11.5 +/- 1.3% (percent of nuclear cells expressing PCNA) to 4.4 +/- 1.3% (mean +/- SEM; p < 0.05). Dexamethasone (3 mg/kg, intraperitoneally) also reduced the PCNA index in bronchial epithelium, from 19.2 +/- 2.3% to 10.9 +/- 2.6% (p < 0.05). Dexamethasone but not apocynin inhibited ozone-induced neutrophil influx. Rats exposed repeatedly to ozone (3.0 ppm, 3 h, on three occasions 48 h apart) expressed a lower PCNA index in bronchial epithelium than did rats exposed only once at 1.9 +/- 0.7% versus 6.0 +/- 0.9%, respectively (p < 0.05). The proliferative epithelial response following a single exposure to ozone is modulated through oxidative and inflammatory mechanisms probably involving neutrophils.
Salmon
M
M
Thoracic Medicine, Imperial College School of Medicine at the National Heart and Lung Institute, London, United Kingdom.
Koto
H
H
Lynch
O T
OT
Haddad
E B
EB
Lamb
N J
NJ
Quinlan
G J
GJ
Barnes
P J
PJ
Chung
K F
KF
D000098:Acetophenones / Q000008:administration & dosage / Q000494:pharmacology*; D000284:Administration, Oral; D000393:Air Pollutants / Q000009:adverse effects*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000494:pharmacology*; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000494:pharmacology*; D000975:Antioxidants / Q000008:administration & dosage / Q000494:pharmacology*; D001980:Bronchi / Q000187:drug effects / Q000473:pathology; D002455:Cell Division / Q000187:drug effects; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D003907:Dexamethasone / Q000008:administration & dosage / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology; D004848:Epithelium / Q000187:drug effects / Q000473:pathology; D005786:Gene Expression Regulation; D005938:Glucocorticoids / Q000008:administration & dosage / Q000494:pharmacology*; D007150:Immunohistochemistry; D007249:Inflammation; D007274:Injections, Intraperitoneal; D008168:Lung / Q000187:drug effects* / Q000473:pathology; D008297:Male; D009249:NADP / Q000037:antagonists & inhibitors; D009504:Neutrophils / Q000187:drug effects; D010083:Oxidants, Photochemical / Q000009:adverse effects*; D010084:Oxidation-Reduction; D010126:Ozone / Q000009:adverse effects*; D018809:Proliferating Cell Nuclear Antigen / Q000032:analysis / Q000235:genetics; D011650:Pulmonary Alveoli / Q000187:drug effects / Q000473:pathology; D051381:Rats; D011914:Rats, Inbred BN; D013997:Time Factors
D000098:Acetophenones; D000393:Air Pollutants; D000893:Anti-Inflammatory Agents; D000894:Anti-Inflammatory Agents, Non-Steroidal; D000975:Antioxidants; D004791:Enzyme Inhibitors; D005938:Glucocorticoids; D010083:Oxidants, Photochemical; D018809:Proliferating Cell Nuclear Antigen; D009249:NADP; D010126:Ozone; D003907:Dexamethasone; C056165:acetovanillone