Functional Toll-like receptor 4 expressed in lactotrophs mediates LPS-induced proliferation in experimental pituitary hyperplasia

SABATINO M; SOSA L; PETITI J; MUKDSI J; MASCANFRONI ID; PELLIZAS CG; GUTIERREZ S; TORRES AI; DE PAUL AL

ELSEVIER INC

Lugar: Amsterdam ; Año: 2013 vol. 319 p. 3020 - 3020

olllikereceptor4(TLR4)hasbeencharacterizedforitsabilitytorecognizebacterialendotoxin lipopolysaccharide(LPS).Consideringthatinfectionsorinflammatory processesmightcontribute totheprogressionofpituitarytumors,weanalyzedtheTLR4functionalrolebyevaluatingtheLPS effect onlactotrophproliferationinprimaryculturesfromexperimentalpituitarytumors,and examinedtheinvolvementofPI3K-AktandNF-κB activationinthiseffect.Inaddition,theroleof 17β-estradiolasapossiblemodulatorofLPS-inducedPRLcellproliferationwasfurther investigated.Inestrogen-inducedhyperplasicpituitaries,LPStriggeredlactotrophcellprolifera- tion. However,endotoxinfailedtoincreasethenumberoflactotrophstakingupBrdUinnormal pituitaries. Moreover,incubationwithanti-TLR4antibodysignificantly reducedLPS-induced lactotrophproliferation,suggestingafunctionalroleofthisreceptor.AsasignofTLR4activation, an LPSchallengeincreasedIL-6releaseinnormalandtumoralcells.By flow cytometry,TLR4 baseline expressionwasrevealedattheplasmame