Potentiation by thyroid hormone of human IFN-γ-induced HLA-DR expression

Hung Yun Lin, Leon J. Martino, Brian D. Wilcox, Faith B. Davis, Jennifer K. Gordinier, Paul J. Davis

Research output: Contribution to journalArticle

46 Citations (Scopus)

Abstract

We have investigated the mechanism by which thyroid hormone potentiates IFN-γ-induced HLA-DR expression. IFN-γ-induced HLA-DR expression requires activation of STAT1α and induction of the Class II trans-activator, CIITA. HeLa and CV-1 cells treated only with L-thyroxine (T4) demonstrated increased tyrosine phosphorylation and nuclear translocation (= activation) of STAT1α; this hormone effect on signal transduction, and T4 potentiation of IFN-γ-induced HLA-DR expression, were blocked by the inhibitors CGP 41251 (PKC) and genistein (tyrosine kinase). Treatment of cells with T4-agarose also caused activation of STAT1α. In the presence of IFN-γ, T4 enhanced cytokine-induced STAT1α activation. Potentiation by T4 of IFN-γ action was associated with increased mRNA for both CIITA and HLA-DR, with peak enhancement at 16 h (CIITA), and 2 d (HLA-DR). T4 increased IFN-γ-induced HLA-DR protein 2.2-fold and HLA-DR mRNA fourfold after 2 d. Treatment with actinomycin D after induction of HLA-DR mRNA with IFN-γ, with or without T4, showed that thyroid hormone decreased the t(1/2) of mRNA from 2.4 to 1.1 h. HeLa and CV-1 cells lack functional nuclear thyroid hormone receptor. 0Tetraiodothyroacetic acid (tetrac) and 3,5,3'-triiodo-thyroacetic acid (triac) blocked T4 potentiation of IFN-γ-induced HLA-DR expression and T4 activation of STAT1α. These studies define an early hormone recognition step at the cell surface that is novel, distinct from nuclear thyroid hormone receptor, and blocked by tetrac and triac. Thus, thyroid hormone potentiation of IFN-γ-induced HLA-DR transcription is mediated by a cell membrane hormone binding site, enhanced activation of STAT1α, and increased CIITA induction.

Original languageEnglish
Pages (from-to)843-849
Number of pages7
JournalJournal of Immunology
Volume161
Issue number2
Publication statusPublished - Jul 15 1998
Externally publishedYes

    Fingerprint

ASJC Scopus subject areas

  • Immunology

Cite this

Lin, H. Y., Martino, L. J., Wilcox, B. D., Davis, F. B., Gordinier, J. K., & Davis, P. J. (1998). Potentiation by thyroid hormone of human IFN-γ-induced HLA-DR expression. Journal of Immunology, 161(2), 843-849.