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Effects of Hyperoxia on Tumor Necrosis Factor α and Groβ Expression in Newborn Rabbit Lungs

Lung volume 181, pages 335–346 (2003)Cite this article

Abstract

Chemokines have been implicated in the pathogenesis of many inflammatory processes, including bronchopulmonary dysplasia in mechanically ventilated premature infants. We hypothesized that early expression of the proinflammatory cytokine, tumor necrosis factor α (TNFα), would be followed by later expression of the downstream chemokine, Groβ, in the oxygen-injured newborn lung. Reverse transcriptase-polymerase chain reaction (RT-PCR) and ribonuclease protection assay (RPA) were used to assess TNFα and Groβ mRNA expression in lung RNA samples from newborn rabbits exposed to >95% O2 for 8–9 days, followed by 60% O2 for a further 2–4 weeks or from control rabbits exposed to air. Four lung samples per condition were collected every 2 days from day 0 to day 14, and at days 22 and 36. Rabbit alveolar macrophages (AM) stimulated in vitro with bacterial lipopolysaccharide served as positive controls (n = 8). Groβ mRNA expression in rabbit lung samples increased with oxygen exposure until day 8, then returned toward baseline levels. This corresponded to previously described elevations in neutrophil number in the lungs. TNFα mRNA expression in lung samples was below the limit of detection by RPA and showed no upregulation in hyperoxic lung samples by RT-PCR. TNFα activity was assessed in lung lavage (n = 2 samples per condition per time) using an L929 cell line bioassay and was not increased in hyperoxic animals. The expression of Groβ mRNA without antecedent or concurrent TNFα mRNA expression or activity makes it unlikely that Groβ in the hyperoxic newborn rabbit lung is elaborated in response to a stimulus by TNFα.

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Authors and Affiliations

  1. Department of Pediatrics, Strong Children’s Research Center, University of Rochester, Rochester, NY 14623, USA

    R. Varughese, J. L. Nayak, M. LoMonaco, M. A. O’Reilly & C. T. D’Angio

  2. Department of Pediatrics, State University of New York at Buffalo, Buffalo, NY, USA

    R. M. Ryan

Authors
  1. R. Varughese
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  2. J. L. Nayak
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  3. M. LoMonaco
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  4. M. A. O’Reilly
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  5. R. M. Ryan
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  6. C. T. D’Angio
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Correspondence to C. T. D’Angio.

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Varughese, R., Nayak, J., LoMonaco, M. et al. Effects of Hyperoxia on Tumor Necrosis Factor α and Groβ Expression in Newborn Rabbit Lungs . Lung 181, 335–346 (2003). https://doi.org/10.1007/s00408-003-1036-8

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  • DOI: https://doi.org/10.1007/s00408-003-1036-8

Keywords

  • Tumor necrosis factor
  • Chemokines
  • Hyperoxia
  • Groβ
  • Bronchopulmonary dysplasia