All‐trans retinoic acid and a novel synthetic retinoid tamibarotene (Am80) differentially regulate CD38 expression in human leukemia HL‐60 cells: possible involvement of protein kinase C‐δ

Journal of Leukocyte Biology: An Official Publication of the Reticuloendothelial Society

关键词: retinoic acid receptor;    endothelial cells;    adhesion;   

DOI  :  10.1189/jlb.0109025

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

ATRAandasyntheticRARagonisttamibarotene(Am80)inducegranulocyticdifferentiationofhumanacuteleukemiaHL‐60cellsandhavebeenusedinantineoplastictherapy.ATRAinducesCD38antigenduringHL‐60celldifferentiation,whichinteractswithCD31antigenonthevascularECsurfaceandmayinducedisadvantagesinthetherapy.WehereexaminedthemechanismsoftheATRA‐mediatedCD38inductionandcomparedthedifferencebetweenATRA‐andtamibarotene‐mediatedinduction.Tamibarotene‐inducedHL‐60celladhesiontoECswas38%lowerthanATRA,andNB4celladhesiontoECsbytamibarotenewasequivalenttoATRA,whichinducedCD38genetranscriptionbiphasicallyinHL‐60cells,theearly‐phaseinductionviaDR‐RAREcontainingintron1,andthedelayed‐phaseinductionviaRARElackingthe5′‐flankingregion.IncontrasttoATRA,tamibaroteneinducedonlytheearly‐phaseinduction,resultinginitslowerCD38inductionthanATRA.APKCδinhibitor,rottlerin,andsiRNA‐mediatedPKCδknockdownsuppressedtheATRA‐inducedCD38promoteractivityofthe5′‐flankingregion,whereasaRARantagonist,LE540,orRARknockdowndidnotaffectit.Cycloheximideandrottlerinsuppressedthedelayed‐phaseinductionofCD38expressionbyATRAbutdidnotaffecttheearly‐phaseinduction.Moreover,ATRA,butnottamibarotene,inducedPKCδexpressionwithoutaffectingitsmRNAstability.ThediminishedeffectoftamibaroteneonCD38‐mediatedHL‐60celladhesiontoECscomparedwithATRAislikelyaresultofthelackofitsdelayed‐phaseinductionofCD38expression,whichmaybeadvantageousinantineoplastictherapy...

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