Journal of Leukocyte Biology: An Official Publication of the Reticuloendothelial Society | |
miRNA‐125b regulates TNF‐α production in CD14+ neonatal monocytes via post‐transcriptional regulation | |
关键词: epigenetics; neonate; sepsis; cord blood; | |
DOI : 10.1189/jlb.1211593 | |
学科分类:生理学 | |
来源: Federation of American Societies for Experimental Biology | |
【 摘 要 】
Neonates,althoughdeficientincellimmunity,frequentlyrevealsepsiswithaugmentedproinflammatoryreactions.Here,wefoundthatneonatalmonocytesproducedsignificantlyhigherTNF‐αmRNAandproteinthanadultmonocytes.AssessmentofthetranscriptionalfactorfoundnosignificantdifferenceofNF‐κBp65levelbetweenneonatalandadultmonocytes.AdditionofActDtoaccessthehalf‐lifeofTNF‐αmRNArevealednosignificantdifferenceoftheLPS‐inducedTNF‐αmRNAhalf‐lifebetweenthem,whereasCHXincreasedneonatalTNF‐αmRNAsignificantly.Thissuggeststhatapost‐transcriptionalmechanisminvolvestheaugmentationofTNF‐αproductionbyneonatalmonocytes.ToexaminewhethermiRNAwasinvolvedinthepost‐transcriptionalregulation,differentialdisplaysofmiRNAarraybetweenneonatalandadultMNCswereperformed,alongwiththediscoveryofhsa‐miR‐103,hsa‐miR‐125b,hsa‐miR‐130a,hsa‐miR‐454‐3p,andhsa‐miR‐542‐3p,whichweregreaterthanatwofolddecreaseorincreaseafterLPStreatmentfor4h.ThefunctionalvalidationidentifiedthatmiR‐125bdecreasedsignificantlyinassociationwithhigherTNF‐αexpressionbyneonatalmonocytesafterLPSstimulation.TransfectionofthemiR‐125bprecursorintoneonatalmonocytessignificantlyrepressedtheTNF‐αmRNAandproteinexpression,suggestingthatmiR‐125bnegativelyregulatesTNF‐αexpressioninneonatalmonocytes.ModulationofmiRNAexpressionmaybeusedtoregulateTNF‐αproductioninnewbornswithalteredproinflammatoryreactions...
【 授权许可】
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