PELLIZAS CLAUDIA GABRIELA
Congresos y reuniones científicas
Título:
A novel mechanism in the regulation of thyroid peroxidase expression involving the NF-kB transcription factor
Autor/es:
NAZAR M; NICOLA JP; PELLIZAS CG; MASINI-REPISO AM
Reunión:
Congreso; XIV Congress of the Latin American Thyroid Society; 2011
Institución organizadora:
Latin American Thyroid Society
Resumen:
Background: Thyroid peroxidase (TPO) is a central enzyme involved in thyroid hormone
synthesis and the main microsomal component for thyroid autoimmunity. NF-κB is a
critical mediator of the action of lipopolysaccharide (LPS) and other agents. We have
proposed that NF-κB regulates thyroid specific gene expression and that LPS induces
thyroglobulin and Na
+
/I
-
symporter expression.
Objective: To analyze the involvement of NF-κB in regulation of TPO expression.
Methods: FRTL-5 thyroid cells treated with TSH, LPS or LPS + TSH, protein (Western-
blot), mRNA (RT-qPCR), promoter activity (luciferase) and ChIP were assayed.
Results: LPS increased TPO expression over the TSH-induced level. An augment of TSH-
induced TPO mRNA was also observed. To evaluate transcriptional activity, a construct of
TPO promoter (420 bp) was transfected into FRTL-5. LPS enhanced the TSH-stimulated
TPO promoter activity. A construct lacking the κB site showed no response to LPS and
reduced activation by TSH. LPS-induced transcriptional activity was suppressed by a NF-
κB inhibitor, BAY, which also repressed TSH-stimulated TPO expression. A similar
inhibition was exerted by BAY on the TPO protein and mRNA level induced by LPS. As
well, quantitative ChIP assay in TSH and LPS-stimulated cells evidenced the binding of
NFκB subunit p65 to the κB site in TPO promoter.
Conclusions: These findings reveal that a novel mechanism involving the NF-κB pathway
mediates the TSH and LPS-stimulated TPO expression including, at least in part, the
transcriptional level. Since NF-κB activation is related to many pathophysiological
processes such as inflammation and autoimmunity, this study favors that NF-κB-induced
modifications in TPO expression could be implicated in thyroid disease.