Potentiation by thyroxine of interferon-γ-induced HLA-DR expression is protein kinase A- and C-dependent

Hung Yun Lin, Harshad R. Thacore, Faith B. Davis, Leon J. Martino, Paul J. Davis

Research output: Contribution to journalArticle

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Abstract

L-Thyroxine (T4) and 3,3',5-L-triiodothyronine (T3) potentiate the antiviral state induced by interferon-γ (IFN-γ) in homologous cells by a mechanism that is dependent upon calcium/phospholipid-dependent protein kinase (PKC). L-T4 and T3 also potentiate induction by IFN-γ of MHC class II HLA-DR antigen expression in HeLa cells. In the present studies of HLA-DR expression, the PKC inhibitor staurosporine (0.1-1 nM) enhanced the expression of HLA-DR when the inhibitor was added simultaneously with IFN- γ, 100 IU/ml. In the presence of IFN-γ and 10-7 M T4, the same concentrations of staurosporine inhibited potentiation of HLA-DR expression by thyroid hormone. A more specific PKC inhibitor, CGP41251 (0.5-5 nM), similarly enhanced HLA-DR expression in the presence of IFN-γ but inhibited thyroid hormone potentiation of antigen expression. Both actions of CGP41251 were suppressed when cells were also treated with phorbol 12-myristate 13- acetate (PMA). A phospholipase C inhibitor, U73122 (1-1000 nM), did not alter the potentiating ability of T4, although it inhibited in a concentration- dependent manner the expression of HLA-DR induced by IFN-γ. The potentiating effect of T4 was much more sensitive to a cyclic AMP-dependent protein kinase (PKA) inhibitor, KT5720 (1-1000 nM), than was the induction of HLA-DR by IFN-γ. The inhibitory effects of KT5720 were reversed by concurrent 8- bromo-cAMP treatment. The calmodulin antagonist W-7 (5-50 μM) did not alter IFN-γ induction of HLA-DR in either the presence or absence of T4. HLA-DR expression in HeLa cells appears to be under PKC-associated inhibition; IFN- γ reverses this inhibition to promote the appearance of the DR antigen. In contrast, potentiation by T4 of induction of HLA-DR by IFN-γ requires activation of PKC. PKA is involved both in DR induction by IFN-γ and in potentiation of the latter by T4. Thus, PKA and PKC have discrete roles in IFN-γ-induced MHC class II antigen expression and its modulation by thyroid hormone.

Original languageEnglish
Pages (from-to)17-24
Number of pages8
JournalJournal of Interferon and Cytokine Research
Volume16
Issue number1
Publication statusPublished - Jan 1996
Externally publishedYes

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HLA-DR Antigens
Cyclic AMP-Dependent Protein Kinases
Thyroxine
Protein Kinase C
Interferons
Thyroid Hormones
Staurosporine
Histocompatibility Antigens Class II
HeLa Cells
Protein Kinases
Reverse Triiodothyronine
8-Bromo Cyclic Adenosine Monophosphate
Antigens
Type C Phospholipases
Calmodulin
Antiviral Agents
Acetates

ASJC Scopus subject areas

  • Immunology
  • Virology
  • Cell Biology

Cite this

Potentiation by thyroxine of interferon-γ-induced HLA-DR expression is protein kinase A- and C-dependent. / Lin, Hung Yun; Thacore, Harshad R.; Davis, Faith B.; Martino, Leon J.; Davis, Paul J.

In: Journal of Interferon and Cytokine Research, Vol. 16, No. 1, 01.1996, p. 17-24.

Research output: Contribution to journalArticle

Lin, Hung Yun ; Thacore, Harshad R. ; Davis, Faith B. ; Martino, Leon J. ; Davis, Paul J. / Potentiation by thyroxine of interferon-γ-induced HLA-DR expression is protein kinase A- and C-dependent. In: Journal of Interferon and Cytokine Research. 1996 ; Vol. 16, No. 1. pp. 17-24.
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AU - Davis, Paul J.

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