The effect of okadaic acid on elastin gene expression in
interstitial lung fibroblasts.
Berk, John L., Nima Massoomi, Meir Krupsky, and Ronald H. Goldstein.
Pulmonary Center and the Department of Biochemistry at Boston
University School of Medicine and the Boston Veterans Administration
Medical Center, Boston, MA 02118
APStracts 3:0135L, 1996.
Okadaic acid (OA), a specific serine\threonine protein phosphatase
inhibitor, down-regulated tropoelastin formation and elastin mRNA
levels in a dose-related and cycloheximide-sensitive fashion in
cultured lung fibroblasts. Treatment with a tyrosine phosphatase
inhibitor at high concentrations did not alter elastin mRNA levels,
however. Nuclear run-on analysis indicated that OA primarily
suppressed elastin gene expression through a transcriptional
mechanism. In contrast to its effects on elastin expression, OA down
-regulated [alpha]1(I) mRNA to significantly lesser degrees. The
mechanism by which OA decreased elastin mRNA levels did not appear to
involve protein kinase C nor share the signaling pathway of IL
-1[beta]. Prolonged treatment with phorbol ester promoted the
inhibitory effects of OA on elastin, as did shorter treatment with
IL-1[beta]. Moreover, transient transfection studies indicated that
OA and IL-1[beta] do not act through the same cis-acting element in
the elastin promoter. Finally, unlike the transient effects of IL
-1[beta], OA induced persistent inhibition of elastin expression by a
transcriptional mechanism. Taken together, these data indicate that
serine\threonine protein phosphorylation can regulate the amount and
composition of extracellular matrix secreted by fibroblasts into the
interstitium of the lung.
Received 21 March 1995; accepted in final form 31 July 1996.
APS Manuscript Number L91-5.
Article publication pending Am. J. Physiol. (Lung Cell. Mol.
Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 29 August 1996