title: Effects of hyperoxia on tumor necrosis factor alpha and Grobeta expression in newborn rabbit lungs.
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 alpha (TNFalpha), would be followed by later expression of the downstream chemokine, Grobeta, in the oxygen-injured newborn lung. Reverse transcriptase-polymerase chain reaction (RT-PCR) and ribonuclease protection assay (RPA) were used to assess TNFalpha and Grobeta 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). Grobeta 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. TNFalpha mRNA expression in lung samples was below the limit of detection by RPA and showed no upregulation in hyperoxic lung samples by RT-PCR. TNFalpha 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 Grobeta mRNA without antecedent or concurrent TNFalpha mRNA expression or activity makes it unlikely that Grobeta in the hyperoxic newborn rabbit lung is elaborated in response to a stimulus by TNFalpha.
authors.affiliation: Department of Pediatrics, Strong Children's Research Center, University of Rochester, NY 14623, USA.
authors.forename: R
authors.initials: R
authors.lastname: Varughese
authors.forename: J L
authors.initials: JL
authors.lastname: Nayak
authors.forename: M
authors.initials: M
authors.lastname: LoMonaco
authors.forename: M A
authors.initials: MA
authors.lastname: O'Reilly
authors.forename: R M
authors.initials: RM
authors.lastname: Ryan
authors.forename: C T
authors.initials: CT
authors.lastname: D'Angio
mesh_terms: D000818:Animals; D000831:Animals, Newborn / Q000378:metabolism*; D001681:Biological Assay; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D054360:Chemokine CXCL1; D019743:Chemokines, CXC / Q000096:biosynthesis*; D004195:Disease Models, Animal; D018496:Hyperoxia / Q000378:metabolism*; D017403:In Situ Hybridization; D036341:Intercellular Signaling Peptides and Proteins / Q000096:biosynthesis*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008168:Lung / Q000378:metabolism* / Q000473:pathology*; D016676:Macrophages, Alveolar / Q000187:drug effects / Q000378:metabolism; D010100:Oxygen / Q000494:pharmacology; D011658:Pulmonary Fibrosis / Q000378:metabolism; D018075:RNA, Complementary / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D011817:Rabbits; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012680:Sensitivity and Specificity; D013223:Statistics as Topic; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis* / Q000187:drug effects
chemical_list: C475829:CXCL1 protein, human; D054360:Chemokine CXCL1; D019743:Chemokines, CXC; D036341:Intercellular Signaling Peptides and Proteins; D008070:Lipopolysaccharides; D018075:RNA, Complementary; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D010100:Oxygen