Nongenomic effect of thyroid hormone on free-radical production in human polymorphonuclear leukocytes

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Abstract

Over the past few years increasing evidence has suggested the nongenomic effects of thyroid hormone, such as the activation of the signal transduction pathways and the activation of nuclear factor-κB by the induction of oxidative stress. The present study was undertaken to investigate the effect of thyroid hormone on human polymorphonuclear leukocytes (PMNLs) which are known as important sources of reactive oxygen species in the circulation. The production of superoxide anion (O2- ) and the activity of myeloperoxidase were determined in the presence and absence of several inhibitors of the signalling pathway. L-Thyroxine (T4), L-3,5,3′-tri-iodothyronine (T3) and L-3,5-di-iodothyronine (T2) stimulated O2 - production in PMNLs in a dose-dependent manner within a few minutes of addition to cells. Thyroid hormone-stimulated O2- production was partially inhibited by pertussis toxin, an inhibitor of GTP-binding G protein, and was completely abolished by the protein kinase C inhibitors calphostin C and Ro-32-0432, and by a calcium chelator (BAPTA; bis-(o-aminophenoxy)ethane-N,N,N',N',-tetra-acetic acid). Thyroid hormone stimulated myeloperoxidase activity and induced 125I- incorporation into PMNLs. Furthermore, thyroid hormone pre-incubation enhanced O2- production for n-formyl-methionyl-leucyl-phenylalanine (FMLP) stimulation. In conclusion, novel nongenomic actions of thyroid hormone, the induction of superoxide anion production and the stimulation of myeloperoxidase activity in PMNLs were demonstrated. The induction of O2- production requires calcium and is mediated by a pertussis toxin-sensitive G protein via stimulation of protein kinase C(s). These results suggest the existence of a membrane-bound binding site for thyroid hormone in PMNLs and a physiological role for thyroid hormone in the cellular defence mechanisms by stimulating free-radical production.

Original languageEnglish
Pages (from-to)121-129
Number of pages9
JournalJournal of Endocrinology
Volume185
Issue number1
DOIs
Publication statusPublished - Apr 1 2005

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology

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