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.
|Number of pages||8|
|Journal||Journal of Interferon and Cytokine Research|
|Publication status||Published - Jan 1996|
ASJC Scopus subject areas
- Cell Biology