Glucocorticoids regulate glutamine synthetase expression in lung
epithelial cells.
Abcouwer, Steve F., Gregory C. Lukaszewicz, Wiley W. Souba.
Department of Surgery, Massachusetts General Hospital, Harvard
Medical School, Boston, Massachusetts
APStracts 2:0150L, 1995.
During septic states efflux of glutamine from the lung increases, a
response sustained by an increase in glutamine synthetase (GS)
activity. We have used a cell culture model employing a rat
epithelial cell line of pulmonary origin (L2 cells) to study the
effect of several hormones and cytokines which mediate the septic
shock response on GS expression. We found that GS mRNA and GS protein
contents increased rapidly and several fold in response to
physiologically relevant levels of the synthetic glucocorticoid
dexamethasone (DEX). In contrast, GS expression was not markedly
induced by E. coli lipopolysaccharide (LPS), cytokines, activated
complement C5a, or prostaglandins. DEX did not alter the kinetics of
GS mRNA decay in the presence of actinomycin D (Actino). The increase
in GS mRNA in response to DEX was completely blocked by RU38486 and
by Actino, but not by cycloheximide (CHX). CHX together with DEX
caused a superinduction of GS mRNA. GS mRNA decay kinetics suggested
that this superinduction is at least in part caused by an
approximately 2-fold increase in GS mRNA half life caused by CHX. In
addition, Actino was found to increase GS mRNA half life by
approximately 50%. Actino plus CHX acted synergistically to cause a
profound inhibition of GS mRNA decay. Our results are consistent with
regulation of lung GS expression via a direct glucocorticoid
receptor-mediated response. In addition, GS mRNA decay in L2 cells
seems to be regulated by two independent mechanisms, one which is
sensitive to CHX and one which is sensitive to Actino.
Received 1 March 1995; accepted in final form 16 August 1995.
APS Manuscript Number L69-5.
Article publication pending Am. J. Physiol. (Lung Cell. Mol.
Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 24 August 1995.