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1、PerspectiveInterleukin-17AnEmergingRoleinLungInflammationJayK.Kolls,SuzanneT.Kanaly,andAlistairJ.RamsayDepartmentofMedicine,SectionofPulmonaryandCriticalCareMedicine,GeneTherapyProgram,LSUHealthSciencesCenter,NewOrleans,Louisiana;andAmgen,Seattle,Washingt
2、onInterleukin(IL)-17isaproinflammatorycytokine,pro-factors(suchasgranulocytecolony-stimulatingfactor)thatducedbyTcells,thatregulatespulmonaryneutrophilemi-canleadtoincreaseinbothmatureneutrophilsandneutro-grationinthecontextofbothlocalgram-negativebacteri
3、alphilprogenitorinthespleenandbonemarrow(6)(Table1).infectionandnow,inareportbyHellingsandcoworkersIL-17mayalsodownregulateinnateantiviralimmunere-inthisissueoftheAJRCMB,toantigenicstimuli(1).sponses.Vacciniavirusvectorsencodingthisfactordis-IL-17isaproi
4、nflammatorycytokineexpressedbyacti-playedincreasedvirulence,mostlikelythroughinhibitionvatedmemoryCD4Tcells.Itwasinitiallydescribedandofantiviralnaturalkillercellcytotoxicity(13),afeatureclonedbyGolsteinandcoworkersandnamedCTLA8(2).previouslyobservedfoll
5、owinginfectionwithrecombinantIL-17shows58%homologywithanopenreadingframeofpoxvirusesexpressingtheTh2cytokinesIL-4(14)orIL-10theT-lymphotropicherpesvirussamirii(viralIL-17),and(15).Interestingly,IL-17alsoskewedantiviralantibodyistheprototypicmemberofafami
6、lyofIL-17–likecytokinesproductiontowardIgG1andIgAisotypes,suggestiveofanamedIL-17A-F(3,4).Thesecytokinesaresecretedpro-Th2-likeresponsetoinfection.teinsrangingfrom150–180aminoacidsandcirculateasThecytoplasmicdomainoftheIL-17receptorlackscon-dimers.Itappe
7、arsthatIL-17familymemberssignalthroughservedsignalingdomainswithothercytokinereceptors(16),afamilyofuniquecognatereceptors;however,thisremainsandthusthesignalingpathwayofIL-17remainsunclear.tobefullyelucidated.IL-17signalsthroughtheIL-17R(3),IL-17hasbeen
8、reportedtoactivateallthreeclassesofMAPaTypeItransmembraneproteinthatisfairlyubiquitouslykinases,includingERK1andERK2,JNK,andP38(17–19).expressedintissues;however,ourlaboratoryhasbeenun-TheIL-17–inducedactivationoftheMAPKpa
