Nongenomic potentiation by thyroid hormone of interferon-induced
antiviral state requires pka and pkc activities .
Lin, Hung-Yun, Harshad R. Thacore, Faith B. Davis, and Paul J. Davis.
Division of Molecular and Cellular Medicine, Department of
Medicine, Albany Medical College and the Stratton VA Medical Center,
Albany, NY 12208, and Department of Microbiology, State University of
New York at Buffalo School of Medicine and Biomedical Sciences,
Buffalo, NY 14214
APStracts 3:0147C, 1996.
Added to HeLa cells previously exposed to recombinant human
interferon-_ (IFN-_) for 20 h, thyroid hormone (L-thyroxine, T4) in
physiological concentrations potentiates in 4 h by more than 100-fold
the antiviral action of IFN-_. We examined protein kinase activities
for their contributions to the mechanism of this post-translational
effect of thyroid hormone. Added concurrently with thyroid hormone,
the protein kinase C (PKC) inhibitor CGP41251 (5 nM) blocked T4
potentiation of IFN-_ action. Co-incubated with CGP41251, phorbol 12
-myristate 13-acetate (PMA) reversed the effect of the inhibitor on
thyroid hormone action. U73122 (10 nM), a phospholipase C inhibitor,
also blocked hormone potentiation. KT5720 (500 nM), a protein kinase
A (PKA) inhibitor, completely inhibited the T4 effect, while 8-bromo
-cyclic AMP restored hormone action in the presence of KT5720. In the
absence of T4, 8-bromo-cyclic AMP and PMA, added together to cells in
the 4 h paradigm, fully reproduced hormone potentiation of the
antiviral effect of IFN-_. Incubated individually with IFN-_-treated
cells, the two agonists had no potentiating action. Thyroid hormone
apparently must activate both PKA and PKC in the nongenomic pathway
of IFN-_ action in order to enhance antiviral activity in HeLa cells.
Received 4 March 1996; accepted in final form 29 April 1996.
APS Manuscript Number C118-6.
Article publication pending Am. J. Physiol. (Cell Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 8 May 96