Pivotal Advance: Arginase‐1‐independent polyamine production stimulates the expression of IL‐4‐induced alternatively activated macrophage markers while inhibiting LPS‐induced expression of inflammatory genes

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

关键词: AAM;    M2;    classically activated macrophage (CAM or M1);    IL‐;    4‐;    regulated genes;    LPS‐;    regulated genes;   

DOI  :  10.1189/jlb.0911453

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

Inmacrophages,basalpolyamine(putrescine,spermidine,andspermine)levelsarerelativelylowbutareincreaseduponIL‐4stimulation.ThisTh2cytokineinducesArg1activity,whichconvertsarginineintoornithine,andornithinecanbedecarboxylatedbyODCtoproduceputrescine,whichisfurtherconvertedintospermidineandspermine.Recently,weproposedpolyaminesasnovelagentsinIL‐4‐dependentE‐cadherinregulationinAAMs.Here,wedemonstrateforthefirsttimethatseveral,butnotall,AAMmarkersdependonpolyaminesfortheirIL‐4‐inducedgeneandproteinexpressionandthatpolyaminedependencyofgenesreliesonthemacrophagetype.Remarkably,Arg1‐deficientmacrophagesdisplayratherenhancedIL‐4‐inducedpolyamineproduction,suggestingthatanArg1‐independentpolyaminesynthesispathwaymayoperateinmacrophages.Ontheothersideofthemacrophageactivationspectrum,LPS‐inducedexpressionofseveralproinflammatorygeneswasincreasedsignificantlyinpolyamine‐depletedCAMs.Overall,weproposeArg1independentlyproducedpolyaminesasnovelregulatorsoftheinflammatorystatusofthemacrophage.Indeed,whereaspolyaminesareneededforIL‐4‐inducedexpressionofseveralAAMmediators,theyinhibittheLPS‐mediatedexpressionofproinflammatorygenesinCAMs...

【 授权许可】

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