title: Irsogladine maleate regulates gap junctional intercellular communication-dependent epithelial barrier in human nasal epithelial cells.
abstract: The airway epithelium of the human nasal mucosa acts as the first physical barrier that protects against inhaled substances and pathogens. Irsogladine maleate (IM) is an enhancer of gastric mucosal protective factors via upregulation of gap junctional intercellular communication (GJIC). GJIC is thought to participate in the formation of functional tight junctions. However, the effects of IM on GJIC and the epithelial barrier in human nasal epithelial cells (HNECs) remain unknown. To investigate the effects of IM on GJIC and the tight junctional barrier in HNECs, primary cultures of HNECs transfected with human telomerase reverse transcriptase (hTERT-HNECs) were treated with IM and the GJIC inhibitors oleamide and 18β-GA. Some cells were pretreated with IM before treatment with TLR3 ligand poly(I:C) to examine whether IM prevented the changes via TLR3-mediated signal pathways. In hTERT-HNECs, GJIC blockers reduced the expression of tight junction molecules claudin-1, -4, -7, occludin, tricellulin, and JAM-A. IM induced GJIC activity and enhanced the expression of claudin-1, -4, and JAM-A at the protein and mRNA levels with an increase of barrier function. GJIC blockers prevented the increase of the tight junction proteins induced by IM. Furthermore, IM prevented the reduction of JAM-A but not induction of IL-8 and TNF-α induced by poly(I:C). In conclusion, IM can maintain the GJIC-dependent tight junctional barrier via regulation of GJIC in upper airway nasal epithelium. Therefore, it is possible that IM may be useful as a nasal spray to prevent the disruption of the epithelial barrier by viral infections and exposure to allergens in human nasal mucosa.
authors: Department of Otolaryngology, Sapporo Medical University School of Medicine, Sapporo, 060-8556, Japan.
authors: Ryo
authors: R
authors: Miyata
authors: Kazuaki
authors: K
authors: Nomura
authors: Takuya
authors: T
authors: Kakuki
authors: Ken-Ichi
authors: K
authors: Takano
authors: Takayuki
authors: T
authors: Kohno
authors: Takumi
authors: T
authors: Konno
authors: Norimasa
authors: N
authors: Sawada
authors: Tetsuo
authors: T
authors: Himi
authors: Takashi
authors: T
authors: Kojima
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D002450:Cell Communication / Q000187:drug effects*; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism*; D017629:Gap Junctions / Q000187:drug effects*; D015870:Gene Expression; D006034:Glycyrrhetinic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D006801:Humans; D016209:Interleukin-8 / Q000096:biosynthesis; D009297:Nasal Mucosa / Q000378:metabolism*; D009829:Oleic Acids / Q000494:pharmacology; D062725:Tight Junction Proteins / Q000235:genetics / Q000378:metabolism; D014227:Triazines / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
chemical_list: D000970:Antineoplastic Agents; D016209:Interleukin-8; D009829:Oleic Acids; D062725:Tight Junction Proteins; D014227:Triazines; D014409:Tumor Necrosis Factor-alpha; C119129:18alpha-glycyrrhetinic acid; C029407:oleylamide; D006034:Glycyrrhetinic Acid; C041836:irsogladine
references: Pancreas. 1997 Oct;15(3):297-303
references: 9336795
references: Aliment Pharmacol Ther. 2010 Apr;31(8):824-33
references: 20132152
references: Cell Tissue Res. 2007 Oct;330(1):63-74
references: 17701057
references: Biomed Res Int. 2013;2013:947072
references: 23509817
references: Cell Tissue Res. 2009 Nov;338(2):283-93
references: 19763625
references: Carcinogenesis. 1996 Jun;17(6):1199-213
references: 8681433
references: J Histochem Cytochem. 2005 May;53(5):611-9
references: 15872054
references: J Periodontal Res. 2015 Aug;50(4):486-93
references: 25244303
references: Biochem Biophys Res Commun. 2005 Jul 29;333(2):502-7
references: 15961066
references: J Allergy Clin Immunol. 2007 Dec;120(6):1233-44; quiz 1245-6
references: 18073119
references: Am J Physiol Cell Physiol. 2004 Jun;286(6):C1213-28
references: 15151915
references: Front Biosci. 1998 Feb 15;3:d208-36
references: 9458335
references: Cell. 1996 Feb 9;84(3):381-8
references: 8608591
references: J Membr Biol. 2007 Aug;218(1-3):1-7
references: 17623229
references: Nat Rev Mol Cell Biol. 2001 Apr;2(4):285-93
references: 11283726
references: Mol Pharmacol. 2008 Aug;74(2):432-42
references: 18477669
references: J Periodontal Res. 2012 Feb;47(1):55-61
references: 21895660
references: Biochim Biophys Acta. 1979 Feb 4;560(1):1-65
references: 216404
references: Exp Cell Res. 1987 Feb;168(2):422-30
references: 2433137
references: Med Mol Morphol. 2009 Dec;42(4):204-11
references: 20033365
references: Jpn J Pharmacol. 1991 Nov;57(3):321-8
references: 1667533
references: Med Electron Microsc. 2003 Sep;36(3):147-56
references: 14505058
references: Exp Cell Res. 2002 May 15;276(1):40-51
references: 11978007
references: Pharmacol Res. 2010 Jun;61(6):489-98
references: 20227502
references: Exp Cell Res. 2004 Aug 1;298(1):1-8
references: 15242756
references: Proc Natl Acad Sci U S A. 1986 Apr;83(8):2473-7
references: 3010311
references: J Membr Biol. 2007 Jun;217(1-3):13-9
references: 17568974
references: Biochim Biophys Acta. 2008 Mar;1778(3):729-56
references: 17950242
references: Histol Histopathol. 2009 Nov;24(11):1463-72
references: 19760595
references: Toxicol Appl Pharmacol. 2011 Jan 1;250(1):29-38
references: 20932985