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.
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.
Poncin
Sylvie
S
Unité de Morphologie Expérimentale, Université catholique de Louvain, Université catholique de Louvain-5251, 52 Avenue East Mounier, Brussels, Belgium.
Lengelé
Benoit
B
Colin
Ides M
IM
Gérard
Anne-Catherine
AC
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
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