title: Nuclear Factor κB1/RelA Mediates Inflammation in Human Lung Epithelial Cells at Atmospheric Oxygen Levels.
abstract: Oxygen levels range from 2% to 9% in vivo. Atmospheric O2 levels (21%) are known to induce cell proliferation defects and cellular senescence in primary cell cultures. However, the mechanistic basis of the deleterious effects of higher O2 levels is not fully understood. On the other hand, immortalized cells including cancer cell lines, which evade cellular senescence are normally cultured at 21% O2 and the effects of higher O2 on these cells are understudied. Here, we addressed this problem by culturing immortalized human bronchial epithelial (BEAS-2B) cells at ambient atmospheric, 21% O2 and lower, 10% O2. Our results show increased inflammatory response at 21% O2 but not at 10% O2. We found higher RelA binding at the NF-κB1/RelA target gene promoters as well as upregulation of several pro-inflammatory cytokines in cells cultured at 21% O2. RelA knockdown prevented the upregulation of the pro-inflammatory cytokines at 21% O2, suggesting NF-κB1/RelA as a major mediator of inflammatory response in cells cultured at 21% O2. Interestingly, unlike the 21% O2 cultured cells, exposure of 10% O2 cultured cells to H2O2 did not elicit inflammatory response, suggesting increased ability to tolerate oxidative stress in cells cultured at lower O2 levels.
authors.affiliation: Department of Environmental Medicine, New York University School of Medicine, Tuxedo, New York.
authors.forename: Lakshmanan
authors.initials: L
authors.lastname: Jagannathan
authors.affiliation: Department of Environmental Medicine, New York University School of Medicine, Tuxedo, New York.
authors.forename: Cynthia C
authors.initials: CC
authors.lastname: Jose
authors.affiliation: Department of Environmental Medicine, New York University School of Medicine, Tuxedo, New York.
authors.forename: Adriana
authors.initials: A
authors.lastname: Arita
authors.affiliation: Department of Environmental Medicine, New York University School of Medicine, Tuxedo, New York.
authors.forename: Thomas
authors.initials: T
authors.lastname: Kluz
authors.affiliation: Department of Environmental Medicine, New York University School of Medicine, Tuxedo, New York.
authors.forename: Hong
authors.initials: H
authors.lastname: Sun
authors.affiliation: Department of Environmental Medicine, New York University School of Medicine, Tuxedo, New York.
authors.forename: Xiaoru
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Environmental Medicine, New York University School of Medicine, Tuxedo, New York.
authors.forename: Yixin
authors.initials: Y
authors.lastname: Yao
authors.affiliation: Division of Allergy and Immunology and Human Genetics, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.|Department of Pediatrics, College of Medicine, University of Cincinnati, Cincinnati, Ohio.
authors.forename: Andrey V
authors.initials: AV
authors.lastname: Kartashov
authors.affiliation: Division of Allergy and Immunology and Human Genetics, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.|Department of Pediatrics, College of Medicine, University of Cincinnati, Cincinnati, Ohio.
authors.forename: Artem
authors.initials: A
authors.lastname: Barski
authors.affiliation: Department of Environmental Medicine, New York University School of Medicine, Tuxedo, New York.
authors.forename: Max
authors.initials: M
authors.lastname: Costa
authors.affiliation: Department of Environmental Medicine, New York University School of Medicine, Tuxedo, New York.
authors.forename: Suresh
authors.initials: S
authors.lastname: Cuddapah
mesh_terms: D049109:Cell Proliferation; D016922:Cellular Senescence; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004847:Epithelial Cells / Q000378:metabolism / Q000473:pathology; D055785:Gene Knockdown Techniques; D006801:Humans; D007249:Inflammation / Q000378:metabolism* / Q000473:pathology; D008168:Lung / Q000378:metabolism* / Q000473:pathology; D010100:Oxygen / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D051996:Transcription Factor RelA / Q000235:genetics* / Q000378:metabolism
chemical_list: D016207:Cytokines; C498143:RELA protein, human; D051996:Transcription Factor RelA; D010100:Oxygen