Ozone induces clear cellular and molecular responses in the mouse lung independently of the transcription-coupled repair status.
The oxidant ozone is a well-known air pollutant, inhalation of which is associated with respiratory tract inflammation and functional alterations of the lung. It is well established as an inducer of intracellular oxidative stress. We investigated whether Cockayne syndrome B, transcription-coupled, repair-deficient mice (Csb(-/-)), known to be sensitive to oxidative stressors, respond differently to ozone than repair-proficient controls (Csb(+/-)). Mice were exposed to 0.8 parts/million ozone for 8 h, and we examined a wide range of biological parameters in the lung at the gene expression, protein, and cellular level 4 h after the ozone exposure. Relevant biological responses to ozone for both repair-deficient Csb(-/-) and repair-proficient Csb(+/-) mice, as determined by biochemical analysis of bronchoalveolar lavage fluid (e.g., increases of polymorphonuclear neutrophils, alkaline phosphatase, macrophage-inflammatory protein-2, and tumor necrosis factor-alpha), pathological examinations, and gene expression (upregulation of oxidative-stress-related genes) analyses were observed. The bronchoalveolar lavage fluid showed significantly more tumor necrosis factor-alpha in repair-deficient Csb(-/-) mice than in repair-proficient Csb(+/-) mice after ozone exposure. In addition, a clear trend was observed toward fewer differentially expressed genes with a lower fold ratio in repair-deficient Csb(-/-) mice than in repair-proficient Csb(+/-) mice. However, repair-deficient Csb(-/-) mice do not respond significantly more sensitively to ozone compared with repair-proficient Csb(+/-) mice at the level of gene expression. We conclude that, under the conditions employed here, although small differences at the transcriptional level exist between repair-proficient Csb(+/-) mice and transcription-coupled repair defective Csb(-/-) mice, these do not have a significant effect on the ozone-induced lung injury.
Kooter
Ingeborg M
IM
National Institute for Public Health and the Environment, Bilthoven, the Netherlands. ingeborg.kooter@tno.nl
Pennings
Jeroen L A
JL
Fokkens
Paul H B
PH
Leseman
Daan L A C
DL
Boere
A John F
AJ
Gerlofs-Nijland
Miriam E
ME
Cassee
Flemming R
FR
Schalk
Johanna A C
JA
Orzechowski
Tom J H
TJ
Schaap
Mirjam M
MM
Breit
Timo M
TM
Dormans
Jan A M A
JA
van Oostrom
Conny T M
CT
de Vries
Annemieke
A
van Steeg
Harry
H
D000818:Animals; D001835:Body Weight; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D003057:Cockayne Syndrome; D045643:DNA Repair Enzymes / Q000235:genetics; D005260:Female; D020869:Gene Expression Profiling; D008168:Lung / Q000378:metabolism* / Q000473:pathology; D008171:Lung Diseases / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009929:Organ Size; D018384:Oxidative Stress / Q000502:physiology*; D010126:Ozone / Q000009:adverse effects*; D000075223:Poly-ADP-Ribose Binding Proteins
D000075223:Poly-ADP-Ribose Binding Proteins; D010126:Ozone; C513075:Ercc6 protein, mouse; D045643:DNA Repair Enzymes