title: Transcriptome profiling of the newborn mouse lung response to acute ozone exposure.
abstract: Ozone pollution is associated with adverse effects on respiratory health in adults and children but its effects on the neonatal lung remain unknown. This study was carried out to define the effect of acute ozone exposure on the neonatal lung and to profile the transcriptome response. Newborn mice were exposed to ozone or filtered air for 3h. Total RNA was isolated from lung tissues at 6 and 24h after exposure and was subjected to microarray gene expression analysis. Compared to filtered air-exposed littermates, ozone-exposed newborn mice developed a small but significant neutrophilic airway response associated with increased CXCL1 and CXCL5 expression in the lung. Transcriptome analysis indicated that 455 genes were down-regulated and 166 genes were up-regulated by at least 1.5-fold at 6h post-ozone exposure (t-test, p < .05). At 24h, 543 genes were down-regulated and 323 genes were up-regulated in the lungs of ozone-exposed, compared to filtered air-exposed, newborn mice (t-test, p < .05). After controlling for false discovery rate, 50 genes were identified as significantly down-regulated and only a few (RORC, GRP, VREB3, and CYP2B6) were up-regulated at 24h post-ozone exposure (q < .05). Gene ontology enrichment analysis revealed that cell cycle-associated functions including cell division/proliferation were the most impacted pathways, which were negatively regulated by ozone exposure, an adverse effect that was associated with reduced bromo-deoxyuridine incorporation. These results demonstrate that acute ozone exposure alters cell proliferation in the developing neonatal lung through a global suppression of cell cycle function.
authors: * Department of Pediatrics and.
authors: Kelsa
authors: K
authors: Gabehart
authors: Kelly A
authors: KA
authors: Correll
authors: Jing
authors: J
authors: Yang
authors: Maureen L
authors: ML
authors: Collins
authors: Joan E
authors: JE
authors: Loader
authors: Sonia
authors: S
authors: Leach
authors: Carl W
authors: CW
authors: White
authors: Azzeddine
authors: A
authors: Dakhama
mesh_terms: D000393:Air Pollutants / Q000633:toxicity*; D000818:Animals; D000831:Animals, Newborn; D049109:Cell Proliferation / Q000187:drug effects; D054360:Chemokine CXCL1 / Q000235:genetics; D054365:Chemokine CXCL5 / Q000235:genetics; D015536:Down-Regulation; D020869:Gene Expression Profiling; D019570:Inhalation Exposure; D008168:Lung / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D010126:Ozone / Q000633:toxicity*; D014132:Trachea / Q000187:drug effects / Q000648:ultrastructure; D059467:Transcriptome / Q000187:drug effects*; D015854:Up-Regulation
chemical_list: D000393:Air Pollutants; D054360:Chemokine CXCL1; D054365:Chemokine CXCL5; C475895:Cxcl1 protein, mouse; C094739:Cxcl5 protein, mouse; D010126:Ozone
keywords: gene expression.; neonatal lung; ozone