RGD Reference Report - 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.

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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.
Authors:	Szabo-Fresnais, N Blondeau, JP Pomerance, M
Citation:	Szabo-Fresnais N, etal., Mol Cell Endocrinol. 2008 Mar 12;284(1-2):28-37. Epub 2008 Jan 8.
RGD ID:	2293762
Pubmed:	PMID:18280640 (View Abstract at PubMed)
DOI:	DOI:10.1016/j.mce.2007.12.017 (Journal Full-text)
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.

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Object Symbol	Species	Term	Qualifier	Evidence	With	Notes	Source	Original Reference(s)
Fos	Rat	response to cAMP		IEP			RGD
Fosl2	Rat	response to cAMP		IEP			RGD
Jun	Rat	response to cAMP		IEP			RGD
Junb	Rat	response to cAMP		IEP			RGD
Fos	Rat	response to cytokine		IEP			RGD
Fosl2	Rat	response to cytokine		IEP			RGD
Jun	Rat	response to cytokine		IEP			RGD
Junb	Rat	response to cytokine		IEP			RGD

Objects Annotated

Genes (Rattus norvegicus)

Fos (Fos proto-oncogene, AP-1 transcription factor subunit)

Fosl2 (FOS like 2, AP-1 transcription factor subunit)

Jun (Jun proto-oncogene, AP-1 transcription factor subunit)

Junb (JunB proto-oncogene, AP-1 transcription factor subunit)

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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.