Bacterial lipopolisaccharide stimulates the TSH dependent thyroglobulin gene expression at transcriptional level by involving TTF-1 and Pax8 transription factors

VELEZ ML; COSTAMAGNA E; KIMURA E; FOZZATTI L; PELLIZAS CG; MONTESINOS MM; LUCERO AM; COLEONI AH; SANTISTEBAN P; MASINI-REPISO AM

ENDOCRINOLOGY

The Endocrine Society

Año: 2006 vol. 147 p. 3270 - 3275

0013-7227

The bacterial lipopolysaccharide (LPS) is a biological activator that induces multiple gene expression in several cell types. LPS has been proposed as an etiopathogenic agent in autoimmune diseases. However, whether LPS affects the expression of autoantigens has not been explored. Thyroglobulin (TG) is a key protein in the thyroid hormonogenesis and one of the major thyroid autoantigens. This study aimed to analyze the action of LPS on the TG gene expression in FRTL-5 thyroid cells. We demonstrated that LPS increased the TSH-induced TG protein and mRNA level. Evidence that the effect of LPS was exerted at transcriptional level was obtained by transfecting the minimal TG promoter. The C element of the TG promoter, which contains sequences for Pax8 and TTF-1 binding, is essential for the TG promoter full expression under TSH stimulation. We observed that the transcriptional activity of a construct containing five tandem repeats of the C site was increased by LPS indicating a possible involvement of the C site in the LPS-induced TG gene transcription. We demonstrated that the TG promoter mutated at the Pax8 or TTF-1 binding element in the C site did not respond to LPS. In band shift assays we found that the Pax8 and TTF-1 binding to the C site was increased by LPS. The Pax8 and TTF-1 mRNA and protein level was augmented by LPS. Our results revealed for the first time the ability of LPS to stimulate the expression of the thyroid antigenic and hormonogenic TG, a finding of potential pathophysiological implication.