Selective expression of prostaglandin h synthase isoforms and
cytosolic phospholipase a2 during retinoic acid-induced
differentiation of rat tracheal epithelial cells.
Hill, Elizabeth M., Thomas Bader, Paul Nettesheim, and Thomas E.
Eling.
Laboratory of Molecular Biophysics and Laboratory of Pulmonary
Pathobiology, National Institute of Environmental Health Sciences,
P.O. Box 12233, Research Triangle Park, N.C. 27709
APStracts 3:0019L, 1996.
Rat tracheal epithelial cells cultured in vitro at an air-liquid
interface can differentiate into a muco-ciliary or squamous phenotype
depending on the presence or absence of retinoic acid (RA). The
airway epithelium is known to produce a number of eicosanoids. We
propose that eicosanoid biosynthesis is dependent on the
differentiation status of the epithelium. Therefore, prostaglandin
production and the expression of cytosolic phospholipase A2 (cPLA2)
and the prostaglandin H synthase (PGHS) isoforms were investigated
during differentiation to these two phenotypes. The major eicosanoid
produced by both phenotypes was prostaglandin E2 (PGE2).
Proliferating undifferentiated cultures produced low levels of PGE2
regardless of retinoid status. Differentiated muco-ciliary cultures
produced high levels of PGE2 (50ng/106cells) whereas differentiated
squamous cultures produced low levels of PGE2 (<5ng/106 cells).
Muco-ciliary cultures expressed high levels of cPLA2 and PGHS-2 mRNA
and protein. In contrast squamous cultures expressed very low levels
of cPLA2 and PGHS-2 transcript and protein. The PGHS-1 isoform was
expressed in squamous but not in muco-ciliary cultures. We
investigated changes in expression of these enzymes during retinoid
treatment of established squamous cultures. Treatment with RA
resulted in a rapid (24hrs) down regulation of PGHS-1 mRNA
expression. However, the cPLA2 and PGHS-2 genes were expressed in
squamous cultures only after 3 days of RA treatment coincident with
redifferentiation of the culture to a muco-ciliary phenotype. These
studies reveal that retinoid-induced differentiation of airway
epithelium into either a muco-ciliary or squamous phenotype results
in profound changes in the expression of cPLA2 and PGHS isozymes
which regulate prostaglandin formation.
Received 25 September 1995; accepted in final form 7 January
1996.
APS Manuscript Number L285-5.
Article publication pending Am. J. Physiol. (Lung Cell. Mol.
Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 8 February 96