title: Peroxiredoxin I null mice exhibits reduced acute lung inflammation following ozone exposure.
abstract: Acute ozone (O(3)) exposure causes oxidative stress leading inflammation in the lung. However, its precise mechanisms are not fully elucidated. Here, we examined the role of peroxiredoxin I (PrxI) in O(3)-induced pulmonary inflammation using PrxI null (PrxI(-/-)) and wild-type (WT) mice. PrxI is known as an antioxidant and also emerged as a potent proinflammatory factor that activates toll-like receptor 4/nuclear factor-kappa B signalling. Both mice were exposed to 2 ppm O(3) for 6 h and their responses to oxidative stress and acute inflammation in the lung were evaluated after 18 h. The O(3) inhalation activated the transcription factor nuclear factor-erythroid 2-related factor 2 and upregulated heme oxygenase-1 mRNA, the typical makers of oxidative stress, to similar extent in both lungs observed after 0 and 4 h, respectively. O(3) exposure induced significantly less pulmonary inflammation in PrxI(-/-) than in WT mice judging from the reduced infiltrations of neutrophils into the lung and the suppressed production of proinflammatory mediators, such as interleukin-6 and keratinocyte chemoattractant in the bronchoalveolar lavage fluids. Our results suggest that PrxI is not an effective protector against O(3)-induced oxidative damages reportedly caused by harmful lipid metabolites but plays a positive role in the initiation of lung inflammation following O(3) exposure.
authors.affiliation: Center for Environmental Health Sciences, National Institute for Environmental Studies, 16-2 Onogawa, Tsukuba 305-8506, Japan. yanagisawa.rie@nies.go.jp
authors.forename: Rie
authors.initials: R
authors.lastname: Yanagisawa
authors.forename: Eiji
authors.initials: E
authors.lastname: Warabi
authors.forename: Ken-Ichiro
authors.initials: K
authors.lastname: Inoue
authors.forename: Toru
authors.initials: T
authors.lastname: Yanagawa
authors.forename: Eiko
authors.initials: E
authors.lastname: Koike
authors.forename: Takamichi
authors.initials: T
authors.lastname: Ichinose
authors.forename: Hirohisa
authors.initials: H
authors.lastname: Takano
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Ishii
mesh_terms: D000208:Acute Disease; D000818:Animals; D005982:Glutathione Transferase / Q000235:genetics / Q000378:metabolism; D051547:Heme Oxygenase-1 / Q000235:genetics / Q000378:metabolism; D018836:Inflammation Mediators / Q000378:metabolism; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D008168:Lung / Q000201:enzymology / Q000276:immunology* / Q000473:pathology; D008264:Macrophages / Q000276:immunology; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D051267:NF-E2-Related Factor 2 / Q000378:metabolism; D009504:Neutrophils / Q000276:immunology; D010126:Ozone; D054464:Peroxiredoxins / Q000172:deficiency* / Q000235:genetics; D011014:Pneumonia / Q000139:chemically induced / Q000201:enzymology* / Q000276:immunology / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015533:Transcriptional Activation; D015854:Up-Regulation
chemical_list: D018836:Inflammation Mediators; D007527:Isoenzymes; D008565:Membrane Proteins; D051267:NF-E2-Related Factor 2; C495636:Nfe2l2 protein, mouse; D012333:RNA, Messenger; D010126:Ozone; D054464:Peroxiredoxins; C489899:Prdx1 protein, mouse; D051547:Heme Oxygenase-1; C496542:Hmox1 protein, mouse; D005982:Glutathione Transferase; C119995:glutathione S-transferase alpha