Tunicamycin inhibits Toll-like receptor-activated inflammation in RAW264.7 cells by suppression of NF-κB and c-Jun activity via a mechanism that is independent of ER-stress and N-glycosylation.

Title
Tunicamycin inhibits Toll-like receptor-activated inflammation in RAW264.7 cells by suppression of NF-κB and c-Jun activity via a mechanism that is independent of ER-stress and N-glycosylation.
Authors
한인옥
Keywords
Tunicamycin ER stress Inflammation
Issue Date
2013
Publisher
EUROPEAN JOURNAL OF PHARMACOLOGY
Series/Report no.
EUROPEAN JOURNAL OF PHARMACOLOGY ; Vol.721 no.1-3 Startpage 294 Endpage 300
Abstract
In thisstudy,weinvestigatedtheeffectoftunicamycinontheproductionofpro-inflammatorymolecules in RAW264.7macrophagecellsinresponsetolipopolysaccharide(LPS)andToll-likereceptor(TLR) agonists. TunicamycincausedareductioninLPS-inducednitricoxide(NO)productionandexpression of inducibleNOsynthase(iNOS),cyclooxygenase-2(COX-2),interleukin-1beta(IL-1β) andtumor necrosis factoralpha(TNF-α). Incontrast,otherERstress-inducingchemicals,suchasA23187and thapsigargin (TG),increasedLPS-inducedCOX-2expressionandhadnoeffectonLPS-inducediNOS,TNF- α or IL-1β expression.Furthermore,theinhibitoryeffectoftunicamycinonLPS-inducedinflammation wasnotinfluenced bysalubrinal, an ERstressinhibitor,suggestingthattheanti-inflammatory effect of tunicamycinisindependentofERstress.Tunicamycinalsoinhibitedtheexpressionofinflammatory molecule mRNAsinducedbystimulationofTLR2(withlipoteichoicacid)orTLR3(withpolyinosinic: polycytidylicacid),whichdonotrequiremyeloiddifferentiationprotein-2(MD2)fortheiractivation. Moreover,inhibitionofLPS-inducediNOSexpressionwasnotinhibitedbycastanospermine,another N-glycosylationinhibitor,suggestingthattheinhibitoryeffectoftunicamycinonLPS-inducediNOS induction islikelyindependentofMD2 N-glycosylation.Tunicamycininhibitednuclearfactor-kappaB (NF-κB) activitybysuppressingLPS-inducednucleartranslocationofp50andsubsequentDNAbindingof p50 andp65totheNF-κB siteoftheiNOSpromoter.Tunicamycinalsoinhibitedthetranscriptional activity ofacAMP-responseelement(CRE)reporter,possiblybyinhibitingc-Junactivation.Therefore,we conclude thattunicamycinrepressesTLR-inducedinflammation throughsuppressionofNF-κB andCRE activity viaamechanismthatisindependentofER-stressand N-glycosylation.
URI
http://dspace.inha.ac.kr/handle/10505/31188
ISSN
0014-2999
Appears in Collections:
Medical School/College of Medicine (의학전문대학원/의과대학) > Medical Science (의학) > Journal Papers, Reports(의학 논문, 보고서)
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