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.

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