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