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Related Experiment Videos

Tumor necrosis factor-alpha and embryonic mouse lung morphogenesis

T Jaskoll1, P D Boyer, M Melnick

  • 1Laboratory for Developmental Genetics, University of Southern California, Los Angeles 90089-0641.

Developmental Dynamics : an Official Publication of the American Association of Anatomists
|October 1, 1994
PubMed
Summary

Tumor necrosis factor-alpha (TNF-alpha) stimulates embryonic lung development and surfactant protein A expression. This cytokine is likely a key mediator in the glucocorticoid-regulated pathway of lung morphogenesis.

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Area of Science:

  • Developmental Biology
  • Immunology
  • Pulmonology

Background:

  • Embryonic and fetal lung development (ontogeny) involves intricate epithelial-mesenchymal interactions.
  • Genes on chromosome 17, specifically the H-2 region, influence lung morphogenesis rate.
  • Hormones and growth factors are critical messengers in morphogenesis.

Purpose of the Study:

  • To investigate the role of tumor necrosis factor-alpha (TNF-alpha) as a mediator of lung morphogenesis.
  • To examine the spatiotemporal localization and effects of TNF-alpha and its receptor in embryonic lung development.

Main Methods:

  • Utilized immunochemical methods.
  • Employed a serumless, chemically defined in vitro model system with embryonic lung primordia.
  • Supplemented cultures with varying doses of TNF-alpha.

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Main Results:

  • Demonstrated specific spatiotemporal localization of TNF-alpha and its receptor in embryonic lungs, both in vivo and in vitro.
  • Showed that TNF-alpha supplementation dose-dependently stimulates branching morphogenesis and surfactant-associated protein (SP-A) expression.
  • Identified time- and glucocorticoid-dependent changes in TNF-alpha immunoreactive proteins, including a novel 40 kDa protein.

Conclusions:

  • Concluded that TNF-alpha is an autocrine/paracrine pulmonary cytokine involved in lung morphogenesis.
  • Proposed TNF-alpha as a component of the glucocorticoid-regulated pathway controlling lung development.
  • Highlighted TNF-alpha's role in stimulating pulmonary morphodifferentiation and histodifferentiation.