​Tumornecrosisfactoralpha(TNF-αorcachectin)isamemberofafamilyofsmallBIOLOGicallyactiveproteinsknownascytokines. TNF-α playsakeyroleintheinnateinflammatoryresponseinvertebrates.WhenmacrophagesandTcellsdetectaninvADIngpathogen,theyproduceTNF-α,triggeringlocalproductionofchemokinesandadditionalcytokines,whichthenattractandactivateleukocytesattheinfectionsite.(1,2,3,4) TNF-αalsoparticipatesinthedevelopmentofacquiredimmunityfromtheinfection.(5)TNF-αplaysaroleinnumerousotherprocessesthroughoutthebody,includingremodelingoftissuesandcausingapoptosisoftumorcells.(6) DysregulationofTNF-αproductionisinvolvedinperiodontaldisease,heartdisease,auto-immuneconditions,andosteoarthritis.(7,8,9,10,11) MessengerRNAforTNF-αhasbeenfoundintissuesofhealthyhumanlABIalsalivaryglands,andtheexpressionlevelsofthemRNAswereeitherup-ordown-regulatedbyadjacentfocalinfiltratinglymphoidcells.(12) 

Theepithelialcellsinthesalivaryglandsareactiveparticipantsintheautoimmune-mediatedprocessofSjögren’ssyndrome,andTNF-αlevelsareincreasedinthatdisease.(12,13) RelationshipsbetweenTNF-αlevelsinbloodandsalivaarenotfullyunderstood.​

1. Czermak,B.J.,Sarma,V.,Bless,N.M.,etal.(1999). InvitroandinvivodependencyofchemokinegenerationonC5aandTNF-α. JImmunol,162(4),2321-25.
2. Tanabe,K.,Matsushima-Nishiwaki,R.,Yamaguchi,S.,etal.(2010). Mechanismsoftumornecrosisfactor-α-inducedinterleukin-6synthesisingliomacells. JNeuroinflammation,7,16.
3. Sternberg,E.M.(2006). Neuralregulationofinnateimmunity:Acoordinatednonspecifichostresponsetopathogens. NatRevImmunol,6(4),318-28.
4. Heller,R.A.,Krönke,M.(1994). Tumornecrosisfactorreceptor-mediatedsignalingpathways. JCellBiol,126(1),5-9.)
5. Mastroeni,P.,Ménager,N.(2003). DevelopmentofacquiredimmunitytoSalmonella. JMedMicrobiol,52(pt6),453-59.
6. Goodsell,D.S.(2006). Themolecularperspective:Tumornecrosisfactor. Oncologist,11(1),83-4.
7. Giannobile,W.V.,Beikler,T.,Kinney,J.S.,etal.(2009).Salivaasadiagnostictoolforperiodontaldisease:Currentstateandfuturedirections. Periodontology2000,50,52-64.
8. Torre-Amione,G.,Kapadia,S.,Lee,J.,etal.(1996). Tumornecrosisfactor-αandtumornecrosisfactorreceptorsinthefailinghumanheart. Circulation,93(4),704-11.
9. Kulkarni,K.,Selesniemi,K,Brown,T.L.(2006).Interferon-gammasensitizesthehumansalivaryglandcellline,HSG,totumornecrosisfactor-alphainducedactivationofdualapoptoticpathways. Apoptosis,11(12),2205-15.
10. Wu,A.J.,Chen,Z.J.,Tsokos,M.etal(1996), Interferon-gammainducedcelldeathinaculturedhumansalivaryglandcellline.JCellPhysiol,167(2),297-304.
11. Fernandes,J.C.,Martel-Pelletier,J.,Pelletier,J.P.(2002).Theroleofcytokinesinosteoarthritispathophysiology. Biorheology,39(1-2),237-46.
12. Sun,D.,Emmert-Buck,M.R.,Fox,P.C.(1998). DifferentialcytokinemRNAexpressioninhumanlabialminorsalivaryglandsinprimarySjögren’ssyndrome. Autoimmunity,28(3),125-37.
13. Fox,R.I.,Kang,H.I,Ando,D.,etal.(1994). CytokinemRNAexpressioninsalivaryglandbiopsiesofSjögren’ssyndrome. JImmunol,152(11),5532-39.

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