解整合素金属蛋白酶-10与疾病活动相关并介导类风湿性关节炎中单核细胞迁移粘附1591 s2 main.pdfVIP

Adisintegrinandmetalloprotease-10iscorrelated

withdiseaseactivityandmediatesmonocyte

migrationandadhesioninrheumatoidarthritis

TAKEOISOZAKI,SHOISHII,SHINICHIRONISHIMI,AIRINISHIMI,NAOOGURO,SHINYASEKI,

YOKOMIURA,YUSUKEMIWA,KOEIOH,YOICHIROTOYOSHIMA,MASANORINAKAMURA,

KATSUNORIINAGAKI,andTSUYOSHIKASAMA

TOKYO,JAPAN

Adisintegrinandmetalloproteases(ADAMs)areafamilyofproteinsthathavebeen

reportedtobeinvolvedinseveralinflammatoryconditions.Weexaminedthesecre-

tionofADAM-10inbiologicalfluidsfrompatientswithrheumatoidarthritis(RA)and

theroleitplaysinmonocytemigration.ADAM-10levelsweremeasuredusing

enzyme-linkedimmunosorbentassaysandimmunofluorescence.Toexaminethe

roleofADAM-10inRAsynovialfluids(SFs),westudiedTHP-1(humanacute

monocyteleukemiacellline)andmonocytechemotaxis.Todeterminewhether

ADAM-10playsaroleincellproliferationintheRAsynovium,weassayedtheprolif-

erationofADAM-10smallinterferingRNA(siRNA)-transfectedRAfibroblast-likesyn-

oviocytes(FLSs).TheADAM-10levelinRAserumwassignificantlyhigherthanthatin

normalserumandwascorrelatedwithadiseaseactivityscoreof28.ADAM-10–

depletedRASFsshowedadecreaseinTHP-1andmonocytemigratoryactivity

comparedwiththatofsham-depletedcontrols.ADAM-10siRNAinhibitedmonocyte

adhesiontoRAFLSs.Finally,blockingADAM-10secretioninRAFL