Up-Regulation of Interleukin-9 and the Interleukin-9-Associated Calcium-Activated Chloride Channel hCLCA1 in Nasal Mucosa Following In Vivo Allergen Challenge 英文参考文献.docVIP

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Up-Regulation of Interleukin-9 and the Interleukin-9-Associated Calcium-Activated Chloride Channel hCLCA1 in Nasal Mucosa Following In Vivo Allergen Challenge 英文参考文献.doc

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Up-Regulation of Interleukin-9 and the Interleukin-9-Associated Calcium-Activated Chloride Channel hCLCA1 in Nasal Mucosa Following In Vivo Allergen Challenge 英文参考文献

ORIGINAL ARTICLE Up-RegulationofInterleukin-9andtheInterleukin-9- AssociatedCalcium-ActivatedChlorideChannelhCLCA1in NasalMucosaFollowingInVivoAllergenChallenge Hans-PeterHauber,MD,CelineBergeron,MD,MasaoToda,MD,MarioKontolemos,BSc,KennethJ.Holroyd, RoyC.Levitt,MD,andQutaybaHamid,MD,PhD Interleukin(IL)-9isapleiotropicThelper2–typecytokinethathasbeenshowntobeup-regulatedinallergicairwaydisease,including asthma.IL-9hasbeendemonstratedtobeapotentstimulusfortheproductionandsecretionofmucusfromairwayepithelialcells viainductionofacalcium-activatedchloridechannel,hCLCA1.TheobjectiveofthisstudywastoinvestigatetheexpressionofIL-9 andhCLCA1followingallergenchallengeinthenasalmucosaofallergicrhinitispatients.Nasalbiopsieswereobtainedfromallergic rhinitis patients out of allergen season both before (baseline) and after local antigen challenge with either ragweed or diluent (control).ImmunohistochemistryandinsituhybridizationwereusedtoassessIL-9proteinandhCLCA1messengerribonucleicacid. EosinophilsandTcellsweredetectedusingimmunohistochemistry.IL-9andhCLCA1wereverylowatbaseline,andexpressionwas significantlyup-regulatedfollowingragweedchallenge.Whereasthenumberofeosinophilsincreasedafterallergenchallenge,T-cell countsdidnotchangesignificantly.Theresultsofthisstudydemonstratetherelationshipbetweenspecificallergenchallengeand expressionofbothIL-9andhCLCA1,suggestingapossiblemechanismfortheincreasedproductionofmucusfromairwayepithelial cellsinallergicrhinitis. I nterleukin (IL)-9 is a pleiotropic T helper 2–type cytokine that has been shown to be associated with human primary lung epithelial cells is up-regulated by IL-9.9 Transfection of hCLCA1 into human mucoepider- moid cells resulted in up-regulation of the MUC5AC gene.10 Intratracheal administration ofadenovirus-expres- sing antisense ribonucleic acid (RNA) for gob-5 (mCLCA3, themurinecounterpart ofhCLCA1) intomice suppressed mucus overproduction following antigen challenge.10 airway hyperresponsiveness and mucus hy