Potentiation by thyroxine of interferon-γ-induced antiviral state requires PKA and PKC activities

Hung Y. Lin, Harshad R. Thacore, Faith B. Davis, Paul J. Davis

Research output: Contribution to journalArticle

35 Citations (Scopus)

Abstract

Added to HeLa cells previously exposed to recombinant human interferon (IFN)-γ for 20 h, thyroid hormone [L-thyroxine (T4)] in physiological concentrations potentiates the antiviral action of IFN-γ by more than 100- fold in 4 h. We examined protein kinase activities for their contributions to the mechanism of this posttranslational effect of thyroid hormone. Added concurrently with thyroid hormone, the protein kinase C (PKC) inhibitor CGP- 41251 (5 nM) blocked T4 potentiation of IFN-γ action. Coincubated with CGP- 41251, phorbol 12-myristate 13-acetate (PMA) reversed the effect of the inhibitor on thyroid hormone action. U-73122 (10 nM), a phospholipase C inhibitor, also blocked hormone potentiation. KT-5720 (500 nM), a protein kinase A (PKA) inhibitor, completely inhibited the T4 effect, whereas 8- bromoadenosine 3',5'-cyclic monophosphate (8-BrcAMP) restored hormone action in the presence of KT-5720. In the absence of T4, 8-BrcAMP and PMA, added together to cells in the 4-h paradigm, fully reproduced hormone potentiation of the antiviral effect of IFN-γ. Incubated individually with IFN-γ- treated cells, the two agonists had no potentiating action. Thyroid hormone apparently must activate both PKA and PKC in the nongenomic pathway of IFN- γ action to enhance antiviral activity in HeLa cells.

Original languageEnglish
JournalAmerican Journal of Physiology - Cell Physiology
Volume271
Issue number4 40-4
Publication statusPublished - Oct 1996
Externally publishedYes

Keywords

  • antiviral action
  • protein kinase A
  • protein kinase C
  • thyroid hormone

ASJC Scopus subject areas

  • Cell Biology
  • Clinical Biochemistry
  • Physiology
  • Physiology (medical)

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