简介：InordertoanalyzethemechanismofimmunomodulationbyLPSonmurineperitonealsuppressormacrophages,wehave,usingRNaseprotectionassay,checkedthechangesofmRNAexpressionpatternofseveralcytokinegenesduringtheimmuno-modulation.Ithasbeenfoundthat,aftertreatingperitonealsuppressormacrophageswithLPS,mRNAsofIL-12p35,IL-12p40,IL-6andIFN-γarenewlyappeared,whilethoseofIL-1α，IL-1βandIL-1Raareincreasebandthoseofothercytokines,likeTGF-β1andMIFarenotchangedatall.Itseemscertainthatthosecytokines,whoseexpressionisincreasedbyLPSstimulation,mayberesponsibleforthefunctionalchangesofsuppressormacrophagesduringimmuno-modulation.Amongthesechanges,theappearanceofIL-12mRNAmayplayacriticalrole,and,inthisregard,thesynergeticeffectbetewwnIFN-γandLPSontheincreaseofIL-12p35andIL-12p40mRNAexpressionisaninterestingfinding.

简介：cAMPmediatedsignalingmayplayasuppressiveroleinimmuneresponse.WepreviouslyfoundthatthecAMP-elevators(CTxand8-Br-cAMP)inhibitedIL-12,IL-la,IL-6geneexpression,butincreasedthetranscriptionallevelsofIL-10andIL-1RainLPS-treatedmurineperitonealmacrophages.ThepresentstudyexaminedapossiblemolecularmechanisminvolvedincAMPelevators-inducedinhibitionofIL-12p40expressioninresponsetoLPS.OurdatademonstratedthatcAMPelevatorsdownregulatedIL-12p40mRNAexpressionandIL-12pT0productioninmurineperitonealmacrophages.SubsequentstudiesrevealedthatcAMP-elevatorsblockedphosphorylationofp38MAPK,butdidnotaffecttheactivityofNF-κBbindingtoIL-12promoter(-136/-112).ThisisthefirstreportthatcAMPelevatorsinhibitLPS-inducedIL-12productionbyamechanismthatisassociated,atleastinpart,withp38-dependentinhibitionbycAMPsignalingpathways.