MUC1/SEC and MUC1/Y overexpression is associated with inflammation in Sjögren's syndrome

Abstract

ORIGINAL ARTICLEMUC1/SEC and MUC1/Y overexpression is associatedwith inflammation in Sj€ogren’s syndromeHH Sung1,*, I Castro1,*, S Gonz alez2, S Aguilera3, NI Smorodinsky4, AFG Quest1,5, V Bahamondes1,C Alliende1, J Cort es1, C Molina2, U Urz ua1, M-J Barrera1, M Hermoso1, L Herrera1, C Leyton1,M-J Gonz alez11Instituto de Ciencias Biom edicas, Facultad de Medicina, Universidad de Chile, Santiago, Chile;2Facultad de Odontolog ıa,Universidad Mayor, Santiago, Chile;3Departamento de Reumatolog ıa, Cl ınica INDISA, Santiago, Chile;4The Alec and Myra MarmotHybridoma Unit, the Department of Cell Research and Immunology, George S. Wise Faculty of Life Sciences, Tel Aviv University, TelAviv, Israel;5Center for Molecular Studies of the Cell (CEMC), and Advanced Center for Chronic Diseases (ACCDiS), ICBM,Facultad de Medicina, Universidad de Chile, Santiago, ChileOBJECTIVES: To evaluate the expression and localiza-tion of MUC1/SEC and MUC1/Y isoforms in labial sali-vary glands (LSG) from Sj€ogren’s syndrome patients(SS patients), as well as theirin vitroexpression inducedby cytokines.SUBJECTS AND METHODS: Labial salivary gland from27 primary SS patients and 22 non-SS sicca subjectswere studied. Relative MUC1/SEC and MUC1/Y mRNAlevels were determined by qPCR and protein levels byWestern blotting. Induction of mucin mRNAs wasassayedin vitro. Immunohistochemistry was used forlocalization.RESULTS: Relative MUC1/SEC and MUC1/Y mRNA andprotein levels were significantly higher in LSG from SSpatients. These mRNAs were induced by cytokines.MUC1/SEC and MUC1/Y were detected in acini apicalregion of control LSGs, and significant cytoplasmicaccumulation was observed in acini of SS patients.MUC1/Y localized in acinar nuclei and cytoplasm ofinflammatory cells of LSG from SS patients. A strongpositive correlation was observed between cellularMUC1/SEC levels and glandular function determined byscintigraphy.CONCLUSIONS: We show for the first time thatMUC1/SEC and MUC1/Y are expressed in LSG of bothSS patients and non-SS sicca subjects. The observedoverexpression and aberrant localization of MUC1/SECand MUC1/Y and their induction by pro-inflammatorycytokines may favor the perpetuation of the inflamma-tory environment that disrupts the salivary glandularhomeostasis in SS patients.