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Pediatr Res. 2006 Aug;60(2):141-6.

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

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1
Department of Pediatrics, University of Maryland School of Medicine, Baltimore, MD 21201, USA. rviscard@umaryland.edu

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 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.

[Indexed for MEDLINE]

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