CIBICI   14215
CENTRO DE INVESTIGACION EN BIOQUIMICA CLINICA E INMUNOLOGIA
Unidad Ejecutora - UE
artículos
Título:
Functional Toll-Like Receptor 4 Conferring Lipopolysaccharide Responsiveness Is Expressed in Thyroid Cells
Autor/es:
NICOLA JP; VELEZ ML; LUCERO AM; FOZZATTI L; PELLIZAS CG; MASINI-REPISO AM
Revista:
ENDOCRINOLOGY
Editorial:
ENDOCRINE SOC
Referencias:
Lugar: Chavy Chase, MD, USA; Año: 2009 vol. 150 p. 500 - 508
ISSN:
0013-7227
Resumen:
Lipopolysaccharide(LPS),aglycolipidfoundinthecellwallofGram-negativebacteria,exertspleio-tropicbiologicaleffectsindifferentcelltypes.LPSismainlyrecognizedbytheToll-likereceptor(TLR)4/MD2/Clusterofdifferentiation14complex(CD14).WepreviouslydemonstratedthatLPSproducedadirectactiononthyroidcells,includingup-regulationofthyroglobulingeneexpression.ThisworkaimedtostudyfurthertheeffectofLPSonthyroidfunctionandtoelucidatethemechanismbywhichLPSisrecognizedbythethyroidcell.WecoulddetectthetranscriptandproteinexpressionofTLR4,MD2,andCD14inthyroidcells,andthattheseproteinsarelocalizedattheplasmamembrane.Thesodiumiodidesymporter(NIS)isthetransporterinvolvedintheiodideuptake,thefirststepinthyroidhormonogenesis.WedemonstratedthatLPSincreasestheTSH-inducediodideuptakeandNISproteinexpression.TheLPSagonistlipidAreproducedLPSeffect,whereastheLPSantagonist,polymyxinB,abrogatedit.Bytheuseofanti-TLR4blockingantibodiesandthetransientexpressionofTLR4dom-inant-negativeforms,weevidencedtheinvolvementofTLR4intheLPSaction.TheenrichmentofTLR4expressingFisherratthyroidcellline-5(FRTL-5) cellsconfirmedthatTLR4confersLPSresponsiveness tothyroidcells.Inconclusion,werevealedforthefirsttimethatallthecomponentsoftheLPSreceptorcomplexareexpressedinthyroidcells.EvidencethattheeffectsofLPSonrodentthyroidfunctioninvolveTLR4-inducedsignalingwasobtained.ThefactthatthyroidcellsareabletorecognizeandrespondtoLPSsupportsaroleoftheendotoxinasapotentialmodifierofthyroidfunction.(Endocrinology 150:500–508,2009)