Cellular zinc homeostasis is a regulator in monocyte differentiation of HL‐60 cells by 1α,25‐dihydroxyvitamin D3

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

关键词: calcitriol;    TPEN;    cAMP;    transporter;    Zip;    ZnT;   

DOI  :  10.1189/jlb.0409241

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

Itwasreportedpreviouslythatzinc‐deficientmiceshowimpairedlymphopoiesis.Atthesametime,monocytenumbersintheseanimalsareincreased,indicatinganegativeimpactofzinconmonocytedevelopment.Here,weinvestigatetheroleofzinchomeostasisinthedifferentiationofmyeloidprecursorsintomonocytes.Reducedgeneexpressionofseveralzinctransporters,predominantlyfromtheZipfamily,wasobservedduring1α,25‐dihydroxyvitaminD3(1,25D3)‐induceddifferentiationofHL‐60cells.Thiswasaccompaniedbyareductionofintracellular‐freezinc,measuredbyFluoZin‐3.AmplifyingthisreductionwiththezincchelatorTPENorzinc‐depletedcell‐culturemediumenhanced1,25D3‐inducedexpressionofmonocyticsurfacemarkersCD11bandCD14onHL‐60,THP‐1,andNB4cells.Incontrast,differentiationofNB4cellstogranulocyteswasnotzinc‐sensitive,pointingtowardaspecificeffectofzinconmonocytedifferentiation.Further,monocytefunctions,suchasTNF‐αsecretion,phagocytosis,andoxidativeburst,werealsoaugmentedbydifferentiationinthepresenceofTPEN.ThesecondmessengercAMPpromotesmonocytedifferentiation.WecouldshowthatzincinhibitsthecAMP‐synthesizingenzymeadenylatecyclase,andchelationofzincbyTPENincreasescAMPgenerationafterstimulationwiththeadenylatecyclaseactivatorforskolin.Basedonourinvitroresultsandtheinvivoobservationsfromtheliterature,wesuggestamodelinwhichtheintracellular‐freezincconcentrationlimitsACactivity,andthedecreaseofzincafter1,25D3treatmentpromotesdifferentiationbyrelievingACinhibition.Thus,cellularzinchomeostasisactsasanendogenousmodulatorofmonocytedifferentiation...

【 授权许可】

CC BY