Chronic inflammation and fibrosis are hallmarks of lung pathology of newborn Ureaplasma infection. We hypothesized that antenatally acquired Ureaplasma stimulates a chronic inflammatory, profibrotic immune response that contributes to lung injury, altered developmental signaling, and fibrosis. Lung specimens from 125-d gestation baboon newborns ventilated for 14 d that were either infected antenatally with Ureaplasma serovar 1 or noninfected, and 125-d and 140-d gestational controls were obtained from the Baboon BPD Resource Center (San Antonio, TX). Trichrome stain to assess fibrosis and immunohistochemistry for α-smooth muscle actin (α-SMA) and transforming growth factor β1 (TGFβ1) were performed. Lung homogenates were analyzed by enzyme-linked immunosorbent assay (ELISA) for cytokines [tumor necrosis factor α (TNFα), interleukin (IL)-1β, TGFβ1, oncostatin M (OSM), IL-10, and interferon γ (IFNγ)] and the chemokine MCP-1 and by Western blot for Smad2, Smad3, and Smad7. Compared with noninfected ventilated and gestational controls, Ureaplasma-infected lungs demonstrated more extensive fibrosis, increased α-SMA and TGFβ1 immunostaining, and higher concentrations of active TGFβ1, IL-1β, and OSM, but no difference in IL-10 levels. There was a trend toward higher Smad2/Smad7 and Smad3/Smad7 ratios in Ureaplasma lung homogenates, consistent with up-regulation of TGFβ1 signaling. Collectively, these data suggest that a prolonged proinflammatory response initiated by intrauterine Ureaplasma infection contributes to early fibrosis and altered developmental signaling in the immature lung.Abbreviations: α-SMA, α-smooth muscle actin; BPD, bronchopulmonary dysplasia; GC, gestational control; MCP-1, monocyte chemoattractant protein-1; OSM, oncostatin M; UU, Ureaplasma urealyticum
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