Thyroid Peroxidase Gene Expression Is Induced by Lipopolysaccharide Involving Nuclear Factor (NF)-êB p65 Subunit Phosphorylation

MAGALI NAZAR; NICOLA JUAN PABLO; VELEZ MARIA LAURA; PELLIZAS CLAUDIA G; MASINI - REPISO ANA MARIA

ENDOCRINE SOC

Lugar: Chevy Chase, MD ; Año: 2012 vol. 153 p. 6114 - 6114

p>Thyroid peroxidase (TPO), a tissue-specific enzyme expressed in differentiated thyroid follicular cells, is a major antigen that has been linked to autoimmune thyroid disease. We have previously reported the functional expression of the lipopolysaccharide (LPS) receptor Toll-like receptor 4 on thyroid follicular cells. Here we investigated the effect of LPS in TPO expression and analyzed the mechanisms involved. We found a dose-dependent enhancement of TSH-induced TPO expression in response to LPS stimulation. EMSAs demonstrated that LPS treatment increased thyroid transcription factor-1 and -2 binding to the B and Z regions of TPO promoter, respectively. Moreover, LPS increased TSH-stimulated TPO promoter activity. Using bioinformatic analysis, we identified a conserved binding site for transcription nuclear factor-kB (NF-kB) in the TPO promoter. Chemical inhibition of NF-kB signaling and site-directed mutagenesis of the identified kB-cis-acting element abolished LPS stimulation. F