In vivo ozone exposure induces antioxidant/stress-related responses in murine lung and skin.
Lung and skin are the organs directly exposed to environmental pollution. Ozone (O(3)) is a toxic, oxidant air pollutant, and exposure has been shown to induce antioxidant depletion as well as oxidation of lipids and proteins within the outermost skin layer (stratum corneum) and the lung respiratory tract lining fluids (RTLFs). To further define skin and lung responses to O(3) exposure, SKH-1 hairless mice were exposed to either 0.8 ppm of O(3) (a level occasionally reached in very polluted areas) or ambient air 6 h/day for 6 consecutive days. O(3) exposure resulted in the depletion of alpha-tocopherol in lung and plasma and induction in both skin and lung of heme oxygenase 1, cyclooxygenase 2, and proliferating cell nuclear antigen. O(3)-exposed animals showed a similar extent of upregulation of COX-2 and PCNA in lung and skin, whereas HO-1 was more responsive in skin than in lung (7-fold induction vs. 2-fold induction). In addition to these measures of response to oxidative stress, O(3) exposure led to the activation of nuclear factor kappaB measured as IkappaBalpha phosphorylation in both tissues. We conclude that in this model, O(3) at high pollutant levels is able to affect both lung and skin biology, inducing depletion of alpha-tocopherol and inducing stress-related responses in both skin epidermis and respiratory tract epithelium.
Center for Comparative Respiratory Biology and Medicine, University of California Davis, Davis, CA 95616, USA. gvalacchi@ucdavis.edu
Giuseppe
G
Valacchi
Elisa
E
Pagnin
Ana M
AM
Corbacho
Estibaliz
E
Olano
Paul A
PA
Davis
Lester
L
Packer
Carroll E
CE
Cross
D000397:Air Pollution; D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D051546:Cyclooxygenase 2; D006419:Heme Oxygenase (Decyclizing) / Q000378:metabolism; D051547:Heme Oxygenase-1; D007527:Isoenzymes / Q000378:metabolism; D008168:Lung / Q000201:enzymology*; D008565:Membrane Proteins; D051379:Mice; D008812:Mice, Hairless; D018384:Oxidative Stress / Q000502:physiology; D010126:Ozone / Q000633:toxicity*; D010766:Phosphorylation; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D012867:Skin / Q000201:enzymology*; D024502:alpha-Tocopherol / Q000097:blood / Q000378:metabolism; D000097782:NF-kappaB-Inducing Kinase
D000975:Antioxidants; D051546:Cyclooxygenase 2; D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1; D007527:Isoenzymes; D008565:Membrane Proteins; D010126:Ozone; D018809:Proliferating Cell Nuclear Antigen; D011451:Prostaglandin-Endoperoxide Synthases; D017346:Protein Serine-Threonine Kinases; D024502:alpha-Tocopherol; D000097782:NF-kappaB-Inducing Kinase; C496542:Hmox1 protein, mouse