title: Differential interactions between Th1/Th2, Th1/Th3, and Th2/Th3 cytokines in the regulation of thyroperoxidase and dual oxidase expression, and of thyroglobulin secretion in thyrocytes in vitro.
abstract: Hypothyroidism, together with glandular atrophy, is the usual outcome of destructive autoimmune thyroiditis. The impairment in the thyroid function results either from cell destruction or from Th1 cytokine-induced alteration in hormonogenesis. Here, we investigated the impact of the local immune context on the thyroid function. We used two rat thyroid cell lines (PCCL3 and FRTL-5) and human thyrocytes incubated with IL-1alpha/interferon (IFN) gamma together with IL-4, a Th2 cytokine, or with TGF-beta, or IL-10, two Th3 cytokines. We first observed that IL-4 totally blocked IL-1alpha/interferon gamma-induced alteration in dual oxidase and thyroperoxidase expression, and in thyroglobulin secretion. By contrast, TGF-beta and IL-10 had no such effect. They rather repressed thyrocyte function as do Th1 cytokines. In addition, IL-4 blocked IL-10-induced repression of thyrocyte function, but not that induced by TGF-beta. In conclusion, Th1 cytokine- and IL-10-induced local inhibitory actions on thyroid function can be totally overturned by Th2 cytokines. These data provide new clues about the influence of the immune context on thyrocyte function.
authors.affiliation: Unité de Morphologie Expérimentale, Université catholique de Louvain, Université catholique de Louvain-5251, 52 Avenue East Mounier, Brussels, Belgium.
authors.forename: Sylvie
authors.initials: S
authors.lastname: Poncin
authors.forename: Benoit
authors.initials: B
authors.lastname: Lengelé
authors.forename: Ides M
authors.initials: IM
authors.lastname: Colin
authors.forename: Anne-Catherine
authors.initials: AC
authors.lastname: Gérard
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D016207:Cytokines / Q000494:pharmacology*; D000074623:Dual Oxidases; D005420:Flavoproteins / Q000235:genetics*; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D007375:Interleukin-1 / Q000494:pharmacology; D016753:Interleukin-10 / Q000494:pharmacology; D015847:Interleukin-4 / Q000494:pharmacology; D007453:Iodide Peroxidase / Q000235:genetics*; D019255:NADPH Oxidases / Q000235:genetics*; D051381:Rats; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*; D013954:Thyroglobulin / Q000378:metabolism*; D013961:Thyroid Gland / Q000166:cytology / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000494:pharmacology
chemical_list: D016207:Cytokines; D005420:Flavoproteins; D007375:Interleukin-1; D016212:Transforming Growth Factor beta; D016753:Interleukin-10; D015847:Interleukin-4; D007371:Interferon-gamma; D013954:Thyroglobulin; D000074623:Dual Oxidases; D007453:Iodide Peroxidase; D019255:NADPH Oxidases; C431513:DUOX1 protein, human; C524752:Duox1 protein, rat