CIBICI   14215
CENTRO DE INVESTIGACION EN BIOQUIMICA CLINICA E INMUNOLOGIA
Unidad Ejecutora - UE
artículos
Título:
TOLL-LIKE RECEPTOR 4 IS FUNCTIONAL EXPRESSED AT THE PLASMA MEMBRANE CONFERING LIPOPOLYSACCHARIDE RESPONSIVENESS IN THE THYROID CELL
Autor/es:
NICOLA JP; VELEZ ML; LUCERO AM; FOZZATTI L; PELLIZAS CG; MASINI-REPISO AM
Revista:
ENDOCRINOLOGY
Editorial:
The Endocrine Society
Referencias:
Lugar: Chevy Chase, MD, USA; Año: 2008
ISSN:
0013-7227
Resumen:
Lipopolysaccharide (LPS), a glycolipid found in the cell wall of Gram-negative bacteria, exerts pleiotropic biological effects in different cell types. LPS is mainly recognized by the TLR4/MD2/CD14 complex. We previously demonstrated that LPS produce a direct action on thyroid cells including up-regulation of thyroglobulin gene expression. This work aimed to further study the effect of LPS on thyroid function and to elucidate the mechanism by which LPS is recognized by the thyroid cell. We could detect the transcript and protein expression of TLR4, MD2 and CD14 in thyroid cells and that these proteins are localized at the plasma membrane. The sodium iodide symporter (NIS) is the transporter involved in the iodide uptake, the first step in thyroid hormonogenesis. We demonstrated that LPS increases the TSH-induced iodide uptake and NIS protein expression. The LPS agonist lipid A reproduced the LPS effect whereas the LPS antagonist, polymyxin B abrogated it. By the use of anti-TLR4 blocking antibodies and the transient expression of TLR4 dominant negative forms we evidenced the involvement of TLR4 in the LPS action. The enrichment of TLR4 expressing FRTL-5 cells confirmed that TLR4 confers LPS responsiveness to thyroid cells. In conclusion, we revealed for the first time that all the components of the LPS receptor complex are expressed in thyroid cells. Evidence that the effects of LPS on rodent thyroid function involve TLR-4 induced signaling was obtained. The fact that thyroid cells are able to recognize and respond to LPS supports a role of the endotoxin as a potential modifier of thyroid function.