THYROPEROXIDASE GENE EXPRESSION IS STIMULATED BY LIPOPOLYSACCHARIDE (LPS) AT TRANSCRIPCIONAL LEVEL BY INVOLVING A DIFFERENTIAL REGULATION OF TTF-1 AND TTF-2 FACTORS. EVIDENCE FOR TOLL-LIKE RECEPTOR 4 MEDIATION.

VÉLEZ, MARIA LAURA; NICOLA, JUAN PABLO; FOZZATTI, LAURA; LUCERO, ARIEL MAXIMILIANO; MONTESINOS, MARIA DEL MAR; PELLIZAS, CLAUDIA GABRIELA; MASINI-REPISO, ANA MARIA

Santiago de Chile.

Congreso; XII Congreso de la Sociedad Latinoamericana de Tiroides (SLAT).; 2007

Sociedad Latinoamericana de Tiroides (SLAT).

LPS is a constituent of the outer membrane of Gram (-) bacteria that is present in circulation during some infections. LPS is a potent gene inductor, mainly acting on immune cells through the Toll-like receptor (TLR) 4. It has been suggested that LPS plays an etiopathogenic role in autoimmune diseases. Increased expression of autoantigenic proteins was associated with autoimmunity. The expression of thyroperoxidase (TPO) and thyroglobulin (TG) is regulated by TSH mainly by the cAMP pathway involving the thyroid transcription factors TTF-1, TTF-2 and Pax8. We have recently reported that LPS increases TG expression, indicating that LPS is able to modify thyroid-specific gene expression. Together with TG and TSH receptor, TPO is one of the major thyroid autoantigens The aim of the present work was to study the effect of LPS on TPO expression and analyze the mechanism involved. The present study provides evidence that the bacterial LPS increases TPO gene expression by a mechanism involving transcriptional activation. TTF-1 and TTF-2 factors seem to play an important role in LPS action. A differential regulation of TTF-1 and TTF-2 expression was demonstrated. The action of LPS occurs in TSH- or cAMP-stimulated cells, suggesting that a crosstalk between the signaling pathways induced by LPS and TSH/cAMP may occur. Since the cAMP formation is an early event in TSH signaling, a mechanism interacting with cAMP pathway at a distal level of cAMP production could be proposed for LPS effect. It is revealed, for the first time, an involvement of TLR4 in mediating the LPS-induced thyroid-specific gene expression. The results led to suppose that during Gram (-) bacteria-induced infections, LPS could affect the expression of the TPO gene. On the basis of the functional and antigenic properties of TPO, these findings could be of pathophysiological implication.