il 32γ对类风湿性关节炎滑膜成纤维细胞增殖及分泌的影响-effects of il 32 γ on proliferation and secretion of synovial fibroblasts in rheumatoid arthritis.docxVIP

此工作为探究IL-32在RA的炎症反应过程中的作用及其可能的作用机制打下了基础，从而为RA的治疗提供理论基础、实验依据和新的可能的治疗靶标。关键词：类风湿性关节炎；成纤维样滑膜细胞；IL-32γ；治疗靶标AbstractRheumatoidarthritis（RA）isoneofthemostcommonsystemicautoimmunediseaseswithhighdeformity,whichisseriouslyharmfultothehumanhealth.Itispathologicallycharacterizedbysynoviocytes“tumor-like”hyperplasia,inflammatorycellinfiltration,angiogenesisandtheprogressivedestructionofarticularcartilageandbone.ThepathogenesisofRAisverycomplex,itinvolvesintheinteractionbetweenmultiplecells,cellfactorsandsignalpathways,althoughinthepastdozensofyearsthepathologyandphysiologyofRAwaswidelyanddeeplyresearched,italsomadebreakthroughprogress,buttheexactmechanismthatcontributestodiseasepathogenesisarelargelyunknown.Therefore,itisnecessaryforustofurtherresearchandexplorethepathogenesisofRA,andlookformorenewpossibletreatmenttargets.Interleukin-32(IL-32)isanovelinflammatorycytokine，ithassixormoremajorsplicevariants.IthasbeenreportedthatIL-32ishighlyexpressedinRAsynovialtissuebiopsies,butitisnotdetectedintheosteoarthritissynovialtissues.Itpromotescelldifferentiation,affectscellapoptosis,andinducestheexpressionofotherproinflammatorycytokinesandchemokinesviamultiplesignaltransductionpathways,itplaysanimportantroleintheinflammatoryresponse,cardiovasculardiseasesandautoimmunediseasesetc.IL-32γisthelongestisoform,anditexhibitedthehighestbiologicalactivity.TheroleofIL-32γintheproliferationandsecretionofrheumatoidarthritisfibroblast-likesynoviocytes(RA-FLS)andregulationisexploredbyvitroexperiments.It’sdiscoveredthattheoptimalconcentrationofIL-32γtotheproliferationofRA-FLSwas100ng/mlbyMTT.It’salsodiscoveredthatIL-32γpromotedtheproliferationofFLSthroughtheNF-κBsignalingpathwaysbycellularImmunohistochemistry.TheinfluenceofIL-32γtothecellcycleofRA-FLSwasdetectedbyflowcytometryassay(FCM),it’sdiscoveredthatitincressedcellproliferationbypromotingthetransitionofStoG2phase.TheexpressionlevelsofIL-6inRA-FLSafterstimulationwithIL-32γwasdetectedbyRT-PCR,theexpressionlevelsofIL-6inRA-FLSwhichwerepretreatedwit