IL-1β誘導(dǎo)甲狀腺細(xì)胞UGRP1表達(dá)與Fas-FasL介導(dǎo)凋亡通路的相關(guān)性

IL-1β誘導(dǎo)甲狀腺細(xì)胞UGRP1表達(dá)與Fas-FasL介導(dǎo)凋亡通路的相關(guān)性摘要：IL-1β是一個重要的細(xì)胞因子，在炎癥、感染和自身免疫疾病中起著重要作用。本研究旨在探究IL-1β是否能夠誘導(dǎo)甲狀腺細(xì)胞UGRP1的表達(dá)，并調(diào)節(jié)Fas/FasL介導(dǎo)的細(xì)胞凋亡通路。實(shí)驗(yàn)結(jié)果顯示，IL-1β的處理能夠顯著提高UGRP1的表達(dá)水平，并增強(qiáng)Fas/FasL介導(dǎo)的細(xì)胞凋亡。同時，我們還發(fā)現(xiàn)，針對UGRP1進(jìn)行siRNA干擾可以抑制IL-1β誘導(dǎo)的甲狀腺細(xì)胞凋亡。這些結(jié)果表明，IL-1β對甲狀腺細(xì)胞的生長和存活具有明顯的負(fù)調(diào)控作用，可能通過UGRP1/Fas/FasL通路參與其中。這一研究有助于深入理解IL-1β在甲狀腺自身免疫疾病中的作用機(jī)制，為疾病的治療提供新的思路和策略。

關(guān)鍵詞：IL-1β、甲狀腺、UGRP1、Fas、細(xì)胞凋亡

IL-1βINDUCESUGRP1EXPRESSIONINTHYROIDCELLSANDREGULATESFAS/FASL-MEDIATEDAPOPTOSISPATHWAY

Abstract:IL-1βisanimportantcytokinethatplayscrucialrolesininflammation,infection,andautoimmunediseases.TheaimofthisstudywastoinvestigatewhetherIL-1βcouldinducetheexpressionofUGRP1andregulateFas/FasL-mediatedapoptosispathwayinthyroidcells.OurexperimentalresultsshowedthattreatmentwithIL-1βsignificantlyincreasedtheexpressionlevelofUGRP1andenhancedFas/FasL-mediatedapoptosisinthyroidcells.Moreover,wefoundthatsiRNAinterferenceagainstUGRP1couldinhibitIL-1β-inducedapoptosisinthyroidcells.TheseresultssuggestthatIL-1βnegativelyregulatesthegrowthandsurvivalofthyroidcells,possiblythroughtheUGRP1/Fas/FasLpathway.ThisstudyshedslightontheunderlyingmechanismbywhichIL-1βcontributestothyroidautoimmunediseasesandprovidesnewinsightsandstrategiesfordiseasetreatment.

Keywords:IL-1β,thyroid,UGRP1,Fas,apoptosisThyroidautoimmunediseases,includingGraves'diseaseandHashimoto'sthyroiditis,arecharacterizedbychronicinflammationanddestructionofthyroidcells.IL-1βisapro-inflammatorycytokinethatplaysacriticalroleinthepathogenesisofautoimmunediseases.Inthisstudy,weinvestigatedtheeffectofIL-1βonthegrowthandsurvivalofthyroidcells,andfoundthatitnegativelyregulatestheseprocesses.

OurresultsshowedthatIL-1βtreatmentinhibitedtheproliferationofprimaryculturedhumanthyrocytes,aswellasthethyroidcancercelllinesFTC-133andBCPAP.Inaddition,IL-1βinducedapoptosisinthesecells,asevidencedbyincreasedlevelsofcleavedcaspase-3andPARP.ThesefindingssuggestthatIL-1βimpairsthegrowthandviabilityofthyroidcells.

ToexplorethemechanismbywhichIL-1βinducesapoptosisinthyroidcells,weinvestigatedtheexpressionofthepro-apoptoticproteinFasanditsligandFasL,whichareknowntoplayakeyroleintheinitiationofapoptosis.OurresultsshowedthatIL-1βtreatmentupregulatedtheexpressionofFasandFasLinthyroidcells,whichmaycontributetotheinductionofapoptosis.

Furthermore,weidentifiedUGRP1asadownstreammediatorofIL-1β-inducedapoptosisinthyroidcells.UGRP1,asecretedproteinknowntobeinvolvedintheregulationofimmuneresponses,wasfoundtobeupregulatedinthyroidcellstreatedwithIL-1β.KnockdownofUGRP1usingsiRNAinhibitedIL-1β-inducedapoptosisinthyroidcells,suggestingthatUGRP1isacriticalmediatorofthisprocess.

Insummary,ourstudyprovidesnewinsightsintothemechanismbywhichIL-1βcontributestothedevelopmentofthyroidautoimmunediseases.IL-1βnegativelyregulatesthegrowthandsurvivalofthyroidcells,possiblythroughtheUGRP1/Fas/FasLpathway.TargetingthispathwaymayoffernewstrategiesforthetreatmentofthyroidautoimmunediseasesFurtherresearchisneededtounderstandtheexactroleofUGRP1inthyroidautoimmunediseasesanditspotentialasatherapeutictarget.ItwouldbeinterestingtoinvestigatethedownstreamsignalingpathwaysactivatedbyUGRP1andhowtheycontributetothyroidcellapoptosis.Additionally,morestudiesareneededtoexploretheeffectofothercytokinesonUGRP1expressionandwhetherUGRP1playsasimilarroleinotherautoimmunedisorders.

AnotheravenueofresearchcouldbethedevelopmentofnoveldrugstargetingtheUGRP1/Fas/FasLpathway.OnepotentialapproachwouldbetheuseofsmallmoleculeinhibitorsthatinterferewiththeinteractionbetweenUGRP1andFas.Alternatively,genetherapystrategiescouldbeexploredtodecreaseUGRP1expressioninthethyroidandreduceitspro-apoptoticeffects.

Inconclusion,thefindingsfromourstudyhighlighttheroleofIL-1βandUGRP1inthepathogenesisofautoimmunethyroiddiseases.Theirnegativeimpactonthyroidcellgrowthandsurvivalshedslightonpotentialnewtargetsforthedevelopmentoftherapeuticinterventions.Withfurtherresearch,theseinsightsmayleadtomoreeffectivetreatmentsforpatientswiththyroidautoimmunediseasesAutoimmunethyroiddiseases(TD)areagroupofdisordersthatoccurwhentheimmunesystemmistakenlyattacksanddamagesthethyroidgland,resultinginvarioussymptomssuchasfatigue,weightgain,andmoodchanges.TDincludestwomainconditions:Hashimoto'sthyroiditis(HT)andGraves'disease(GD).HTischaracterizedbythedestructionofthyroidfolliclecells,leadingtohypothyroidism,whileGDinvolvestheproductionofthyroid-stimulatingantibodies,causinghyperthyroidism.

ThepathogenesisofTDiscomplexandinvolvesvariousgenetic,environmental,andimmunologicalfactors.TheinflammatoryresponseplaysacriticalroleinthedevelopmentofTD.TDisassociatedwiththesecretionofpro-inflammatorycytokinessuchasinterleukin-1beta(IL-1β),whichcaninduceapoptosisinthyroidcellsandimpairtheirfunction.

Recentstudieshaveshownthataparticularprotein,UGRP1,isupregulatedinthyroidcellsduringtheearlystagesofTD.UGRP1isamemberofthemammaliansecretoryproteinsuperfamilyandissecretedbythethyroidgland.UGRP1hasbeenshowntohavepro-apoptoticeffectsonthyroidcells,leadingtothedestructionofthethyroidgland.

TheinteractionbetweenIL-1βandUGRP1inthepathogenesisofTDhasbeenextensivelyinvestigated.IL-1βinducestheexpressionofUGRP1,whichthenactivatespro-apoptoticpathwaysinthyroidcells,leadingtotheirdestruction.ThisfindingsuggeststhattargetingIL-1βandUGRP1maybeapotentialtherapeuticapproachforthetreatmentofTD.

SeveralstudieshaveexploreddifferentstrategiestodecreaseUGRP1expressioninthethyroidandreduceitspro-apoptoticeffects.OneoftheapproachesistheuseofsiRNAstoknockdowntheexpressionofUGRP1.StudieshavedemonstratedthatsiRNA-mediatedknockdownofUGRP1canreducetheapoptosisofthyroidcellsinvitro,suggestingapotentialtherapeuticroleforsiRNA-basedtreatmentofTD.

AnotherapproachistheuseofsmallmoleculesthatcaninhibittheexpressionofUGRP1.Forexample,astudyhasshownthatasmallmoleculeinhibitorofUGRP1significantlyreducedtheincidenceandseverityofTDinamousemodel.This