INVESTIGADORES
PELLIZAS Claudia Gabriela
artículos
Título:
Bacterial lipopolysaccharide increases thyroglobulin gene expression involving TTF-1 and Pax8 transcription factors
Autor/es:
VELEZ ML; COSTAMAGNA E; KIMURA E; FOZZATTI L; PELLIZAS CG; MONTESINOS MM; LUCERO AM; COLEONI AH; SANTISTEBAN P; MASINI-REPISO AM
Revista:
ENDOCRINOLOGY
Editorial:
HighWire Press
Referencias:
Año: 2006 vol. 147 p. 3270 - 3275
ISSN:
0013-7227
Resumen:
The bacterial lipopolysaccharide (LPS) is a biological activator
that induces expression of multiple genes 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 thyroid hormonogenesis and one
of the major thyroid autoantigens. This study aimed to analyze
the action of LPS on TG gene expression in Fisher rat
thyroid cell line FRTL-5 thyroid cells. We demonstrate that
LPS increases the TSH-induced TG protein and mRNA level.
Evidence that the effect of LPS is exerted at the transcriptional
level was obtained by transfecting the minimal TG promoter.
The C element of the TG promoter, which contains
sequences for paired box domain transcription factor 8 (Pax8)
and thyroid transcription factor (TTF)-1 binding, is essential
for full TG promoter expression under TSH stimulation. The
transcriptional activity of a construct containing five tandem
repeats of the C site is increased by LPS, indicating a possible
involvement of the C site in the LPS-induced TG gene transcription.
We demonstrate that the TG promoter mutated at
the Pax8 or TTF-1 binding element in the C site does not
respond to LPS. In band shift assays, binding of Pax8 and
TTF-1 to the C site is increased by LPS. The Pax8 and TTF-1
mRNA and protein levels are augmented by LPS. The halflives
of TG, Pax8, and TTF-1 are increased in endotoxintreated
cells. Our results reveal the ability of LPS to stimulate
the expression of TG, a finding of potential pathophysiological
implication. (Endocrinology 147: 32603275, 2006)