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8of RHEUMATOLOGY 1
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H öHMaToSöinon Meow tou TLR3 au^avei in auv9ean Kai npoKaXei nupnviKH avaKaiavoMH iou auioavTiYövou Ro52/TRIM21 ae Eni9nXiaKa Kuiiapa ZieXoYövwv Aöevwv (EKZA), Meaw iou Movonaiiou iwv IvrepQepovwv Tunou I
NiKÖAaoQ X. KupiaKiSriQ, BSc*, Euaia9ia K. Kai^oyswpyou, PhD*, BaaiAiKri X. roupZn, MD, rswpyioQ E. MnaAxaxZnQ, PhD1, A8aväaioQ r. T(iou$aQ, MD,
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Tr|A: 210 7462512-14
Fax: 2107462664
Email: agtzi@med.uoa.gr
Corresponding author;
Athanasios G. Tzioufas
Professor of Rheumatology - Immunology
Department of Pathophysiology, School of Medicine
University of Athens, Greece
Tel: 210 7462512-14
Fax: 2107462664
Email: agtzi@med.uoa.gr
onMavTiKa, n Ka9uorepn|Jevn au^nan £K0paanQ iou mRNA t|Q Ro52/TRIM21 auvoöeüinKe anö avaKaiavoMH t|Q npwieTvnQ Ro52/TRIM21 oiov nupqva, anö eva npöiuno nou npoaoMOiaZei oe XP^an iou nupnviaKOu ae apKeieq KOUKiöeQ nou eKieivoviai ae öXo to eupoQ iou nupqva. Ta Ka9uaTepnMeva auia 0aivöMeva MeaoXaßouvTai KupiwQ anö inv napaY^YH IFNß, önwQ KaiaMapiupeiiai anö inv eKKpian t|Q avTiaroixnc iviep0epövnQ anö ia EKZA Kai anö eiöiKa neipaMaia avaaioXnQ. H anMaToööTnan Meaw iou TLR3 eixe napöMoia eniöpaan ae EKZA nou eixav Xn09ei anö aa9eveiQ
Ae^eiQ-KXeiöiä: Auioavoaia, auioavTiauMaia, auvöpoMo Sjögren, TLR, ZieXoYövoi AöeveQ
of RHEUMATOLOGY i
E Л Л H N I К H РЕУМАТОЛОПА 2015
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Еимпераара: H GПматоöóтr|GП |j£gw тои TLR3 pu9|jíZei тг^ éкфрaGП тшv auтоavтlYÓvwv ап0 EKLA eмпÀéкоvтaç та |JOvопáтla тг|С фuGlкпç avoGÎaç Gтпv aú^HGH тг|С é^paGriç тшv auтоavтlYÓvшv au^v gtouç фÀeYмaívоvтeç igtoùç Kai пl9avá Kai Grr|v éK0eGn touç Gто av0G0П0lПTlкó GÚGтпмa.
Mediterr J Rheumatol 2015; 26(1): 77-79
H IHMATOAOTHIH MEIQ TOY TLR3 AYEANEI TH IYN0EIH KAI nROKAAEI nYPHNIKH ANAKATANOMH TOY AYTOANTIEONOY R052/TRiM21 IE EH0HAIAKA KYTTAPAIIEAOEONQN AAENQN (EKIA), MEIQ TOY MONOnATlOYTON INTEPOEPONQN TYnOY i SiGNAL TRANSDUCTiON ViA TLR3 iNCREASES SYNTHESiS AND NUCLEAR TRANSLOCATiON OF AUTOANTiGEN RO52/TRiM21 iN EPiTHELiAL CELLS OF SALiVARY GLANDS THROUGH THE iNTERFERON i PATHWAY
Signal transduction via TLR3 increases synthesis and nuclear translocation of autoantigen Ro52/TRIM21 in epithelial cells of salivary glands through the interferon I pathway
Nikolaos X. Kyriakidis, BSc*, Eustathia K. Kapsogeorgou, PhD*, Vasiliki X.Gourzi, MD, Georgios E. Baltatzis1, PhD, Athanasios G. Tzioufas, MD
Department of Pathophysiology, department of Morbid Physiology, and 2Laboratory of Morbid Anatomy, EKPA Medical School, Athens.
* These authors contributed equally to the study.
ABSTRACT
Objective: Upregulated expression of Ro52/TRIM21, R06O/TROVE2 and La/SSB autoantigens has been described at the salivary gland epithelial cells (SGEC) of patients with Sjogren's syndrome (SS). SGECs, the key regulators of autoimmune SS responses, express high levels of surface functional TLR3, whereas Ro52/TRIM21 negatively regulates TLR3-mediated inflammation. Herein, we investigated the effect of TLR3-signaling on the expression of Ro52/TRIM21, as well as Ro60/TROVE2 and La/SSB autoantigens, by SGECs.
Methods: The effect of TLR3- or TLR4-stimulation on autoantigen expression was evaluated by polyI:C or LPS treatment, respectively, of SGEC-lines (10 from SS-patients, 12 from non-SS controls) or HeLa cells, followed by analysis of mRNA and protein expression. Results: PolyI:C, but not LPS, resulted in a two-step induction of Ro52/TRIM21 mRNA expression by SGECs, a 12-fold at 6-hrs followed by a 2.5-fold increment at 24-48-hrs, whereas it induced a late 2-fold upregulation of Ro60/TROVE2 and La/SSB mRNAs at 48-hrs. Although, protein expression levels were not significantly affected, the late upregulation of Ro52/TRIM21 mRNA was accompanied by protein redistribution, from nucleolar-like pattern to multiple coarse dots spanning throughout nucleus. These late phenomena were significantly mediated by IFN|3 production, as attested by cognate secretion and specific inhibition experiments and associated with IRF3 degradation. TLR3-signaling had similar effects on SGECs obtained from SS patients and controls, whereas it did not affect the expression of these autoantigens in HeLa cells. Conclusion: TLR3-signaling regulates the expression of autoantigens by SGECs, implicating innate immunity pathways in their overexpression at inflamed tissues and possibly in their exposure to immune system.
Mediterr J Rheumatol 2015; 26(1): 77-79
Keywords: Autoimmunity, autoantibodies, Sjögren's syndrome, Toll-like Receptor, salivary glands
