title: Functional estrogen receptors alpha and beta are expressed in normal human salivary gland epithelium and apparently mediate immunomodulatory effects.
abstract: Salivary gland epithelial cells (SGECs) have been shown to participate in immunological responses and have been implicated in the pathogenesis of Sjögren's syndrome (SS). Experimental evidence from animal models indicates that estrogen deficiency may also participate in SS pathogenesis. However, the expression and functionality of the estrogen receptors alpha (ERalpha) and beta (ERbeta) in normal human salivary epithelium is unknown. To investigate these points, formalin-fixed, paraffin-embedded specimens and cultured non-neoplastic SGEC lines derived from nine minor salivary gland (MSG) biopsies with normal histology were studied. Immunohistochemical analyses detected the epithelial expression of ERalpha, ERbeta1, and ERbeta2 protein isoforms both in MSG tissues and in cultured SGECs. Such epithelial expression was verified by immunoblotting of various ER proteins in cellular extracts of cultured SGECs (full-length-ERalpha, ERalpha-Delta3, ERbeta1-long, ERbeta1-short, and ERbeta2-long isoforms). Estrogens did not induce growth or apoptosis in cultured SGECs. However, similarly to other cellular systems, treatment of cultured SGECs with estrogens (17beta-estradiol and the ERalpha- and ERbeta-selective agonists propylpyrazole-triol and diarylpropiolnitrile, respectively) inhibited the interferon-gamma-inducible expression of intercellular adhesion molecule-1. This finding corroborated the functionality of ER expressed by SGEC. Our results suggest that salivary epithelium expresses constitutively functional ERalpha and ERbeta proteins that apparently mediate immunomodulatory effects.
authors.affiliation: Department of Pathophysiology, National and Kapodistrian University of Athens, Athens, Greece.
authors.forename: Maria
authors.initials: M
authors.lastname: Tsinti
authors.forename: Eva
authors.initials: E
authors.lastname: Kassi
authors.forename: Penelope
authors.initials: P
authors.lastname: Korkolopoulou
authors.forename: Efstathia
authors.initials: E
authors.lastname: Kapsogeorgou
authors.forename: Paraskevi
authors.initials: P
authors.lastname: Moutsatsou
authors.forename: Efstratios
authors.initials: E
authors.lastname: Patsouris
authors.forename: Menelaos N
authors.initials: MN
authors.lastname: Manoussakis
mesh_terms: D017304:Annexin A5; D017209:Apoptosis; D002457:Cell Extracts; D002460:Cell Line; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002478:Cells, Cultured; D004396:Coloring Agents; D004791:Enzyme Inhibitors; D004847:Epithelial Cells / Q000276:immunology; D004958:Estradiol / Q000494:pharmacology; D047628:Estrogen Receptor alpha / Q000819:agonists / Q000032:analysis / Q000276:immunology*; D047629:Estrogen Receptor beta / Q000819:agonists / Q000032:analysis / Q000276:immunology*; D004967:Estrogens / Q000494:pharmacology; D006801:Humans; D015151:Immunoblotting; D056747:Immunomodulation / Q000276:immunology*; D018799:Intercellular Adhesion Molecule-1 / Q000187:drug effects; D007371:Interferon-gamma / Q000494:pharmacology; D008024:Ligands; D009570:Nitriles / Q000494:pharmacology; D010636:Phenols; D011419:Propidium; D011422:Propionates / Q000494:pharmacology; D020033:Protein Isoforms / Q000032:analysis / Q000276:immunology; D011720:Pyrazoles / Q000494:pharmacology; D012470:Salivary Glands, Minor / Q000166:cytology / Q000276:immunology*; D013778:Tetrazolium Salts; D013844:Thiazoles; D019010:Vascular Cell Adhesion Molecule-1 / Q000187:drug effects
chemical_list: C486182:2,3-bis(4-hydroxyphenyl)-propionitrile; D017304:Annexin A5; D002457:Cell Extracts; D004396:Coloring Agents; D004791:Enzyme Inhibitors; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D004967:Estrogens; D008024:Ligands; D009570:Nitriles; D010636:Phenols; D011422:Propionates; D020033:Protein Isoforms; D011720:Pyrazoles; D013778:Tetrazolium Salts; D013844:Thiazoles; D019010:Vascular Cell Adhesion Molecule-1; C486184:4,4',4''-(4-propyl-((1)H)-pyrazole-1,3,5-triyl) tris-phenol; D018799:Intercellular Adhesion Molecule-1; D011419:Propidium; D004958:Estradiol; D007371:Interferon-gamma; C022616:thiazolyl blue