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1、InternationalImmunopharmacology7(2007)70–77www.elsevier.com/locate/intimpAnti-inflammatoryeffectsofshortchainfattyacidsinIFN-γ-stimulatedRAW264.7murinemacrophagecells:InvolvementofNF-κBandERKsignalingpathwaysJin-SunPark,Eun-JungLee,Jae-ChulLee,Won-KiKim,Hee
2、-SunKim⁎DepartmentofNeuroscienceandMedicalResearchInstitute,CollegeofMedicine,EwhaWomansUniversity,Mok-6-dong911-1,Yangchun-Ku,Seoul158-710,SouthKoreaReceived18July2006;receivedinrevisedform26August2006;accepted29August2006AbstractTheoveractivationofmacroph
3、agescausesabnormalcelldeathandchronicinflammatorydiseases.Therefore,themodulationofmacrophage-mediatedcytotoxicityisexpectedtobecomeanewtherapeuticstrategyforvariousinflammatorydiseases.Inthisstudy,threetypesofshortchainfattyacids(sodiumbutyrate(NaB),sodium
4、phenylbutyrate(NaPB),sodiumphenylacetate(NaPA))werefoundtohaveanti-inflammatoryeffectsinIFN-γ-stimulatedRAW264.7cells.TheyinhibitedtheexpressionofiNOS,TNF-α,andIL-6inducedbyIFN-γ,whiletheyenhancedtheexpressionoftheanti-inflammatorycytokine,IL-10.Theirpotenc
5、yasanti-inflammatoryagentswasintheorderofNaBNNaPBNNaPA.FurthermechanisticstudiesrevealedthesethreeagentstorepresstheDNAbindingandtranscriptionalactivitiesofNF-κB,whichisanimportantmodulatorofinflammation.Inaddition,theseagentsrepressedtheIFN-γ-inducedERK1/2
6、phosphorylationwithoutaffectingtheJak/STATactivities.ThepotencyofNF-κBandERKinhibitionwasalsointheorderofNaBNNaPBNNaPA.TheresultssuggestthattheNF-κBandERKsignalingpathwaysareatleastinpartinvolvedintheanti-inflammatoryactivitiesoftheseSCFAs.ConsideringthatSC
7、FAsarenormallypresentinthebodyandhavefewsideeffects,theymightbepromisingagentsforthepreventionand/ortreatmentofvariousinflammatorydiseases.©2006ElsevierB.V.Allrightsreserved.Keywords:Shortchainfattyacids;Macrophage;Cytokine;iNOS;NF-κB;ERK1.IntroductionMacro
8、phagesplayimportantrolesinvariousinflam-matoryresponses,immunity,hostdefense,andtissuerepair.Onceactivated,macrophagessecretealargeAbbreviations:SCFA,shortchainfattyacid;NaB,sodiumbutyrate;NaPB,sodiump
