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
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 -