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

Pediatr Res. 2006 Aug;60(2):141-6. doi: 10.1203/01.pdr.0000228322.73777.05.


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 alpha-smooth muscle actin (alpha-SMA) and transforming growth factor beta1 (TGFbeta1) were performed. Lung homogenates were analyzed by enzyme-linked immunosorbent assay (ELISA) for cytokines [tumor necrosis factor alpha (TNFalpha), interleukin (IL)-1beta, TGFbeta1, oncostatin M (OSM), IL-10, and interferon gamma (IFNgamma)] 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 alpha-SMA and TGFbeta1 immunostaining, and higher concentrations of active TGFbeta1, IL-1beta, 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 TGFbeta1 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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Actins / analysis
  • Animals
  • Animals, Newborn
  • Chemokine CCL2 / analysis
  • Chemokine CCL2 / metabolism
  • Cytokines / analysis
  • Cytokines / metabolism
  • In Vitro Techniques
  • Inflammation Mediators / analysis
  • Inflammation Mediators / metabolism*
  • Lung / chemistry
  • Lung / microbiology
  • Lung / pathology
  • Muscle, Smooth
  • Papio
  • Premature Birth / microbiology*
  • Premature Birth / pathology
  • Pulmonary Fibrosis / metabolism
  • Pulmonary Fibrosis / microbiology
  • Pulmonary Fibrosis / pathology*
  • Respiration, Artificial
  • Respiratory Tract Infections / metabolism
  • Respiratory Tract Infections / pathology
  • Smad Proteins / analysis
  • Smad Proteins / metabolism
  • Transforming Growth Factor beta / analysis
  • Transforming Growth Factor beta / metabolism
  • Ureaplasma Infections / immunology
  • Ureaplasma Infections / metabolism
  • Ureaplasma Infections / pathology*
  • Ureaplasma urealyticum*


  • Actins
  • Chemokine CCL2
  • Cytokines
  • Inflammation Mediators
  • Smad Proteins
  • Transforming Growth Factor beta