miRNA‐125b regulates TNF‐α production in CD14+ neonatal monocytes via post‐transcriptional regulation

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

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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