title: Interferon-gamma increased epithelial barrier function via upregulating claudin-7 expression in human submandibular gland duct epithelium.
abstract: Tight junctions (TJs) are necessary for salivary gland function and may serve as indicators of salivary gland epithelial dysfunction. IgG4-related disease (IgG4-RD) is a newly recognized fibro-inflammatory condition which disrupts the TJ associated epithelial barrier. The salivary glands are one of the most frequently involved organs in IgG4-RD, however, changes of the TJ associated epithelial barrier in salivary gland duct epithelium is poorly understood. Here, we investigated the regulation and function of TJs in human submandibular gland ductal epithelial cells (HSDECs) in normal and IgG4-RD. We examined submandibular gland (SMG) tissue from eight control individuals and 22 patients with IgG4-RD and established an HSDEC culture system. Immunohistochemistry, immunocytochemistry, western blotting, and measurement of transepithelial electrical resistance (TER) were performed. Claudin-4, claudin-7, occludin, and JAM-A were expressed at the apical side of the duct epithelium in submandibular gland (SMG) tissue and at the cell borders in HSDECs of normal and IgG4-RD. The expression and distribution of TJs in SMG tissue were not different in control individuals and patients with IgG4-RD in vivo and in vitro. Although interferon-gamma (IFNγ) generally disrupts the integrity and function of TJs, as manifested by decreased epithelial barrier function, IFNγ markedly increased the epithelial barrier function of HSDECs via upregulation of claudin-7 expression in HSDECs from patients with IgG4-RD. This is the first report showing an IFNγ-dependent increase in epithelial barrier function in the salivary gland duct epithelium. Our results provide insights into the functional significance of TJs in salivary gland duct epithelium in physiological and pathological conditions, including IgG4-RD.
authors.affiliation: Department of Otolaryngology, Sapporo Medical University School of Medicine, S1W16, Chuo-ku, Sapporo, 060-8543, Japan.
authors.forename: Ayumi
authors.initials: A
authors.lastname: Abe
authors.affiliation: Department of Otolaryngology, Sapporo Medical University School of Medicine, S1W16, Chuo-ku, Sapporo, 060-8543, Japan. kent@sapmed.ac.jp.
authors.forename: Kenichi
authors.initials: K
authors.lastname: Takano
authors.affiliation: Department of Cell Science, Research Institute for Frontier Medicine, Sapporo Medical University School of Medicine, Sapporo, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Kojima
authors.affiliation: Department of Otolaryngology, Sapporo Medical University School of Medicine, S1W16, Chuo-ku, Sapporo, 060-8543, Japan.
authors.forename: Kazuaki
authors.initials: K
authors.lastname: Nomura
authors.affiliation: Department of Otolaryngology, Sapporo Medical University School of Medicine, S1W16, Chuo-ku, Sapporo, 060-8543, Japan.|Department of Cell Science, Research Institute for Frontier Medicine, Sapporo Medical University School of Medicine, Sapporo, Japan.
authors.forename: Takuya
authors.initials: T
authors.lastname: Kakuki
authors.affiliation: Department of Otolaryngology, Sapporo Medical University School of Medicine, S1W16, Chuo-ku, Sapporo, 060-8543, Japan.|Department of Cell Science, Research Institute for Frontier Medicine, Sapporo Medical University School of Medicine, Sapporo, Japan.
authors.forename: Yakuto
authors.initials: Y
authors.lastname: Kaneko
authors.affiliation: Department of the Gastroenterology, Rheumatology and Clinical Immunology, Sapporo Medical University School of Medicine, Sapporo, Japan.
authors.forename: Motohisa
authors.initials: M
authors.lastname: Yamamoto
authors.affiliation: Department of the Gastroenterology, Rheumatology and Clinical Immunology, Sapporo Medical University School of Medicine, Sapporo, Japan.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Takahashi
authors.affiliation: Department of Otolaryngology, Sapporo Medical University School of Medicine, S1W16, Chuo-ku, Sapporo, 060-8543, Japan.
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Himi
mesh_terms: D000328:Adult; D000368:Aged; D001327:Autoimmune Diseases / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D016022:Case-Control Studies; D002478:Cells, Cultured; D057167:Claudins / Q000235:genetics* / Q000378:metabolism; D017097:Electric Impedance; D004848:Epithelium / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D005260:Female; D015870:Gene Expression; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D007371:Interferon-gamma / Q000378:metabolism* / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D013363:Submandibular Gland / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D062725:Tight Junction Proteins / Q000235:genetics / Q000378:metabolism; D019108:Tight Junctions / Q000378:metabolism; D015854:Up-Regulation
chemical_list: C473255:CLDN7 protein, human; D057167:Claudins; D007074:Immunoglobulin G; D062725:Tight Junction Proteins; D007371:Interferon-gamma
keywords: Claudin; Epithelial barrier function; IgG4-related disease; Submandibular gland; Tight junctions