Ontogeny of cyclooxygenase-1 and cyclooxygenase-2 gene expression in ovine lung

Timothy S. Brannon, Amy N. MacRitchie, Marina A. Jaramillo, Todd S. Sherman, Ivan S. Yuhanna, Linda R. Margraf, Philip W. Shaul

Research output: Contribution to journalArticle

50 Scopus citations

Abstract

Prostacyclin is a key mediator of pulmonary vascular and parenchymal function during late fetal and early postnatal life, and its synthesis in whole lung increases during that period. The rate-limiting enzyme in prostacyclin synthesis in the developing lung is cyclooxygenase (COX). We investigated the ontogeny and cellular localization of COX-1 (constitutive) and COX-2 (inducible) gene expression in lungs from late-gestation fetal lambs, 1-wk-old newborn lambs (NB1), and 1- to 4-mo-old newborn lambs (NB2). COX-1 mRNA abundance rose progressively from fetal to NB1 to NB2, increasing 12-fold overall. In parallel, immunoblot analysis revealed a progressive increase in COX-1 protein, rising fourfold from fetal lambs to NB2. COX-2 mRNA levels increased fivefold from fetal to NB1 but were similar in NB1 and NB2. However, COX-2 protein was not detectable by immunoblot analysis in any age group. Immunohistochemistry for COX-1 showed intense immunostaining in endothelial cells at all ages. COX-1 was also expressed in airway epithelium at all ages, with a greater number of epithelial cells staining positively in NB2 compared with fetal and NB1 groups. In addition, COX-1 was expressed in airway smooth muscle from NB1. COX-2 immunostaining was absent in all age groups. These findings indicate that there is differential expression of COX- 1 and COX-2 in the developing lung and that the enzymes are expressed in a cell-specific manner. The developmental upregulation in COX-1 may optimize the capacity for prostaglandin-mediated vasodilation, bronchodilation, and surfactant synthesis in the newborn lung.

Original languageEnglish (US)
Pages (from-to)L66-L71
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume274
Issue number1 18-1
StatePublished - Jan 1 1998

Keywords

  • Airway epithelium
  • Airway smooth muscle
  • Immunohistochemistry
  • Prostacyclin
  • Vascular endothelium

ASJC Scopus subject areas

  • Physiology
  • Pulmonary and Respiratory Medicine
  • Physiology (medical)
  • Cell Biology

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    Brannon, T. S., MacRitchie, A. N., Jaramillo, M. A., Sherman, T. S., Yuhanna, I. S., Margraf, L. R., & Shaul, P. W. (1998). Ontogeny of cyclooxygenase-1 and cyclooxygenase-2 gene expression in ovine lung. American Journal of Physiology - Lung Cellular and Molecular Physiology, 274(1 18-1), L66-L71.