ThisdiagramillustratestheopposingeffectsthatProepithelin(PEPI)andtheelastasedigestfragments,theepithelins(EPIa-g),haveonepithelialgrowthandneutrophilactivation.PEPI(alsoknownasprogranulin,PC-cellderivedgrowthfactorandacrogranin)iscomprisedofsevenfullandonehalfEPImotifseparatedbyalinker.NMRstudiesindicatethatEPI’sarecompactglobularstructuresleADIngtothecurrentsuggestionofastringofbeadsasillustratedhere.Theepithelinsarehighlyhomologous6kDapeptideswithsignificantconservationinplants,insects,wormsandmammals.TheEPI’sstimulateepithelialcellsecretionofIL-8,whichinturnstimulatesneutrophilstosecreteelastase.PEPIalsoinhibitstheinhibitionofsecretoryleukocyteproteaseinhibitor(SLPI)andstimulatesthegrowthofepithelialcellsleadingtowoundclosure.SLPIissecretedbyepithelialcell,neutrophilsandmacrophages.SLPIinhibitselastaseandcathepsinGandtheinhibitionofSLPIfromfreeradicalsproducedbyneutrophilsinthebloodstreamaspartofthebalancebetweenwoundrepairandwoundcleaning.SLPIbindstoPEPIandpreventselastasefromcleavingthevariouslinkerregionsbetweentheEPI’s.SLPIalsobindsandblockstheproteaseactivitiesofelastase.Uncheckedelastaseleadstoimparedwoundhealing.InsummaryPEPIandSLPI,normallyprevalentepithelialcells,protecttheepitheliafromrovingneutrophils.InjurycausesareductioninSLPIleadingtothecleavageofPEPIintotheindividualEPI’s.TheindividualEPI’sactivatetheneutrophilsandgeneratethewoundcleaningresponse.AsthelevelofSLPIreturnstheamountofPEPIisrestoredandtheswitchfrominflammationtorepairoccurs. Contributor: REFERENCES:ZhuJ,NathanC,JinW,SimD,AshcroftGS,WahlSM,LacomisL,Erdjument-BromageH,TempstP,WrightCD,DingA.Conversionofproepithelintoepithelins:rolesofSLPIandelastaseinhostdefenseandwoundrepair.Cell.2002Dec13;111(6):867-78.