Modulation of human monocyte/macrophage activity by bDMARDS: an in vitro study

OBENG Joyce Afrakoma; Angela Amoruso; CAMASCHELLA Gian Luca Ermanno; DANIELE SOLA; BRUNELLESCHI Sandra; Luigia Grazia FRESU

doi:10.1016/j.ejphar.2016.03.028

Modulation of human monocyte/macrophage activity by bDMARDS: an in vitro study

OBENG Joyce Afrakoma
, Angela Amoruso
, CAMASCHELLA Gian Luca Ermanno
, DANIELE SOLA
, BRUNELLESCHI Sandra
, Luigia Grazia FRESU

Research output: Contribution to journal › Article › peer-review

Abstract

Tocilizumab,etanerceptandabataceptarebiologicaldrugsusedinthetherapyofRheumatoidArthritis (RA). Theirmechanismofactioniswelldocumentedbuttheirdirecteffectsonhumanmonocytes/ macrophageshavenotbeenfullyinvestigated.Theobjectiveofthisstudywastoevaluate in vitro the influence ofthesedrugsonmonocytes/macrophagesfromhealthyvolunteers. Human monocyteswereisolatedfromhealthyanonymousvolunteersandculturedassuchordif- ferentiatedtomonocyte-derivedmacrophages(MDMs).Theeffectoftocilizumab,etanerceptandaba- tacept (atconcentrationssimilartothoseinplasmaofpatients)onsuperoxideanionproduction,matrix metalloproteinase-9(MMP-9)geneexpressionandactivity,PeroxisomeProliferator-ActivatedReceptor (PPAR)γ expressionandcellphenotypewasevaluated. Exposure ofmonocytes/macrophagestotocilizumab,etanerceptorabataceptresultedinasignificant decrease ofthePMA-inducedsuperoxideanionproduction.Interestingly,theexpressionofPPARγ was significantly increasedonlybytocilizumab,whileetanerceptwastheonlyoneabletosignificantly re- duce MMP-9geneexpressionandinhibittheLPS-inducedMMP-9activityinmonocytes.Wheneta- nerceptandabataceptwereaddedtothedifferentiatingmedium,bothsignificantly reducedtheamount of CD206þMDM. This studydemonstratesthatetanercept,abataceptandtocilizumabaffectdifferentlyhuman monocytes/macrophages.Inparticular,theIL-6antagonisttocilizumabseemstobemoreeffectivein inducing ananti-inflammatory phenotypeofmonocytes/macrophagescomparedtoetanerceptand abatacept, alsoinlightoftheup-regulationofPPARγ whose anti-inflammatoryeffectsarewellre- cognised.

Original language	English
Pages (from-to)	33-37
Number of pages	5
Journal	European Journal of Pharmacology
Volume	780
DOIs	https://doi.org/10.1016/j.ejphar.2016.03.028
Publication status	Published - 2016

Keywords

Monocytes/macrophages Inflammation Biological drugs

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10.1016/j.ejphar.2016.03.028

http://hdl.handle.net/11579/78027

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title = "Modulation of human monocyte/macrophage activity by bDMARDS: an in vitro study",

abstract = "Tocilizumab,etanerceptandabataceptarebiologicaldrugsusedinthetherapyofRheumatoidArthritis (RA). Theirmechanismofactioniswelldocumentedbuttheirdirecteffectsonhumanmonocytes/ macrophageshavenotbeenfullyinvestigated.Theobjectiveofthisstudywastoevaluate in vitro the influence ofthesedrugsonmonocytes/macrophagesfromhealthyvolunteers. Human monocyteswereisolatedfromhealthyanonymousvolunteersandculturedassuchordif- ferentiatedtomonocyte-derivedmacrophages(MDMs).Theeffectoftocilizumab,etanerceptandaba- tacept (atconcentrationssimilartothoseinplasmaofpatients)onsuperoxideanionproduction,matrix metalloproteinase-9(MMP-9)geneexpressionandactivity,PeroxisomeProliferator-ActivatedReceptor (PPAR)γ expressionandcellphenotypewasevaluated. Exposure ofmonocytes/macrophagestotocilizumab,etanerceptorabataceptresultedinasignificant decrease ofthePMA-inducedsuperoxideanionproduction.Interestingly,theexpressionofPPARγ was significantly increasedonlybytocilizumab,whileetanerceptwastheonlyoneabletosignificantly re- duce MMP-9geneexpressionandinhibittheLPS-inducedMMP-9activityinmonocytes.Wheneta- nerceptandabataceptwereaddedtothedifferentiatingmedium,bothsignificantly reducedtheamount of CD206{\th}MDM. This studydemonstratesthatetanercept,abataceptandtocilizumabaffectdifferentlyhuman monocytes/macrophages.Inparticular,theIL-6antagonisttocilizumabseemstobemoreeffectivein inducing ananti-inflammatory phenotypeofmonocytes/macrophagescomparedtoetanerceptand abatacept, alsoinlightoftheup-regulationofPPARγ whose anti-inflammatoryeffectsarewellre- cognised.",

keywords = "Monocytes/macrophages Inflammation Biological drugs, Monocytes/macrophages Inflammation Biological drugs",

author = "\{Joyce Afrakoma\}, OBENG and Angela Amoruso and \{Gian Luca Ermanno\}, CAMASCHELLA and DANIELE SOLA and BRUNELLESCHI Sandra and FRESU, \{Luigia Grazia\}",

year = "2016",

doi = "10.1016/j.ejphar.2016.03.028",

language = "English",

volume = "780",

pages = "33--37",

journal = "European Journal of Pharmacology",

issn = "0014-2999",

publisher = "Elsevier BV",

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TY - JOUR

T1 - Modulation of human monocyte/macrophage activity by bDMARDS: an in vitro study

AU - Joyce Afrakoma, OBENG

AU - Amoruso, Angela

AU - Gian Luca Ermanno, CAMASCHELLA

AU - SOLA, DANIELE

AU - Sandra, BRUNELLESCHI

AU - FRESU, Luigia Grazia

PY - 2016

Y1 - 2016

N2 - Tocilizumab,etanerceptandabataceptarebiologicaldrugsusedinthetherapyofRheumatoidArthritis (RA). Theirmechanismofactioniswelldocumentedbuttheirdirecteffectsonhumanmonocytes/ macrophageshavenotbeenfullyinvestigated.Theobjectiveofthisstudywastoevaluate in vitro the influence ofthesedrugsonmonocytes/macrophagesfromhealthyvolunteers. Human monocyteswereisolatedfromhealthyanonymousvolunteersandculturedassuchordif- ferentiatedtomonocyte-derivedmacrophages(MDMs).Theeffectoftocilizumab,etanerceptandaba- tacept (atconcentrationssimilartothoseinplasmaofpatients)onsuperoxideanionproduction,matrix metalloproteinase-9(MMP-9)geneexpressionandactivity,PeroxisomeProliferator-ActivatedReceptor (PPAR)γ expressionandcellphenotypewasevaluated. Exposure ofmonocytes/macrophagestotocilizumab,etanerceptorabataceptresultedinasignificant decrease ofthePMA-inducedsuperoxideanionproduction.Interestingly,theexpressionofPPARγ was significantly increasedonlybytocilizumab,whileetanerceptwastheonlyoneabletosignificantly re- duce MMP-9geneexpressionandinhibittheLPS-inducedMMP-9activityinmonocytes.Wheneta- nerceptandabataceptwereaddedtothedifferentiatingmedium,bothsignificantly reducedtheamount of CD206þMDM. This studydemonstratesthatetanercept,abataceptandtocilizumabaffectdifferentlyhuman monocytes/macrophages.Inparticular,theIL-6antagonisttocilizumabseemstobemoreeffectivein inducing ananti-inflammatory phenotypeofmonocytes/macrophagescomparedtoetanerceptand abatacept, alsoinlightoftheup-regulationofPPARγ whose anti-inflammatoryeffectsarewellre- cognised.

AB - Tocilizumab,etanerceptandabataceptarebiologicaldrugsusedinthetherapyofRheumatoidArthritis (RA). Theirmechanismofactioniswelldocumentedbuttheirdirecteffectsonhumanmonocytes/ macrophageshavenotbeenfullyinvestigated.Theobjectiveofthisstudywastoevaluate in vitro the influence ofthesedrugsonmonocytes/macrophagesfromhealthyvolunteers. Human monocyteswereisolatedfromhealthyanonymousvolunteersandculturedassuchordif- ferentiatedtomonocyte-derivedmacrophages(MDMs).Theeffectoftocilizumab,etanerceptandaba- tacept (atconcentrationssimilartothoseinplasmaofpatients)onsuperoxideanionproduction,matrix metalloproteinase-9(MMP-9)geneexpressionandactivity,PeroxisomeProliferator-ActivatedReceptor (PPAR)γ expressionandcellphenotypewasevaluated. Exposure ofmonocytes/macrophagestotocilizumab,etanerceptorabataceptresultedinasignificant decrease ofthePMA-inducedsuperoxideanionproduction.Interestingly,theexpressionofPPARγ was significantly increasedonlybytocilizumab,whileetanerceptwastheonlyoneabletosignificantly re- duce MMP-9geneexpressionandinhibittheLPS-inducedMMP-9activityinmonocytes.Wheneta- nerceptandabataceptwereaddedtothedifferentiatingmedium,bothsignificantly reducedtheamount of CD206þMDM. This studydemonstratesthatetanercept,abataceptandtocilizumabaffectdifferentlyhuman monocytes/macrophages.Inparticular,theIL-6antagonisttocilizumabseemstobemoreeffectivein inducing ananti-inflammatory phenotypeofmonocytes/macrophagescomparedtoetanerceptand abatacept, alsoinlightoftheup-regulationofPPARγ whose anti-inflammatoryeffectsarewellre- cognised.

KW - Monocytes/macrophages Inflammation Biological drugs

UR - https://iris.uniupo.it/handle/11579/78027

U2 - 10.1016/j.ejphar.2016.03.028

DO - 10.1016/j.ejphar.2016.03.028

M3 - Article

SN - 0014-2999

VL - 780

SP - 33

EP - 37

JO - European Journal of Pharmacology

JF - European Journal of Pharmacology

ER -

Modulation of human monocyte/macrophage activity by bDMARDS: an in vitro study

Abstract

Keywords

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