Antenatal Ureaplasma urealyticum respiratory tract infection stimulates proinflammatory, profibrotic responses in the preterm baboon lung

Rose M. Viscardi, Sergei P. Atamas, Irina G. Luzina, Jeffrey D. Hasday, Ju Ren He, Patricia J. Sime, Jacqueline J. Coalson, Bradley A. Yoder

Research output: Contribution to journalArticle

66 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)141-146
Number of pages6
JournalPediatric Research
Volume60
Issue number2
DOIs
StatePublished - Aug 2006

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health

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