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Activation of the cAMP pathway synergistically increases IL-1-induced IL-6 gene expression in FRTL-5 thyroid cells: involvement of AP-1 transcription factors.

Abstract：

:Interleukin-6 (IL-6) is a multifunctional cytokine involved in autoimmune thyroid diseases such as Hashimoto's thyroiditis and Graves' disease. IL-6 is produced by infiltrating immune cells and by thyrocytes. In the latter cell type, secretion of IL-6 is stimulated notably by interleukin-1 (IL-1), thyroid-stimulating hormone (TSH) or forskolin (Fk), a cAMP elevating agent. We report here that Fk and IL-1 synergistically enhance IL-6 mRNA expression in FRTL-5 thyroid cells by mechanisms involving the cAMP/PKA pathway, and both stabilization of the IL-6 mRNA and activation of the IL-6 promoter. Point mutations or deletions of the main transcription factor binding sites in the IL-6 promoter indicated that the synergistic effect was mainly mediated by the AP-1 site, and that the CRE site contributed to this effect. The DNA binding activity of AP-1 transcription factors and the expression of c-Fos and Fra-2 proteins, were all enhanced when the cAMP and IL-1 signalling pathways were both stimulated. These findings contribute to elucidating the synergistic mechanisms that regulate IL-6 secretion by thyroid cells, and suggest that such mechanisms may be involved in the development of thyroid autoimmune disorders.

journal_name

Mol Cell Endocrinol

journal_title

Molecular and cellular endocrinology

authors

Szabo-Fresnais N,Blondeau JP,Pomérance M

doi

10.1016/j.mce.2007.12.017

subject

Has Abstract

pub_date

2008-03-12 00:00:00

pages

28-37

issue

1-2

eissn

0303-7207

issn

1872-8057

pii

S0303-7207(08)00004-X

journal_volume

284

pub_type

杂志文章

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