title: Irsogladine maleate influences the response of gap junctional intercellular communication and IL-8 of human gingival epithelial cells following periodontopathogenic bacterial challenge.
abstract: Gingival epithelial cells first encounter periodontopathogenic bacteria and their metabolic products to produce inflammatory cytokines. Gap junctional intercellular communication (GJIC) is thought to play a critical role in cellular coordination in tissue homeostasis. Gap junctions are structured by connexins (CXs). GJIC response of gingival epithelial cells to the bacteria may be involved in the initiation of periodontal disease. Irsogladine maleate (IM) is known to enhance GJIC through cAMP. In the present study, we examined an effect of IM on GJIC response and on interleukin-8 (IL-8) levels in human gingival epithelial cells (HGEC) exposed to a periodontopathogenic bacterium, Actinobacillus actinomycetemcomitans, and its outer membrane protein (OMP) 29 in order to test the hypothesis that IM has the ability to modulate GJIC and inflammatory responses of gingival epithelial cells to periodontopathogenic bacteria. IM countered the OMP29-induced reduction of GJIC, CX43 levels and cAMP levels in HGEC. The simultaneous addition of OMP29 and dibutyryl cAMP also abrogated the repression of GJIC by OMP29. Furthermore, IM obviated the increase in IL-8 levels in HGEC stimulated by whole live A. actinomycetemcomitans and by OMP29. These findings suggest that IM counters the OMP29-induced GJIC reduction in HGEC through cAMP. IM may eliminate initial perturbation of gingival epithelial cells by regulating responses of GJIC and IL-8 to periodontopathogenic bacterial exposure.
authors.affiliation: Department of Periodontal Medicine, Division of Frontier Medical Science, Hiroshima University Graduate School of Biomedical Sciences, Hiroshima 734-8553, Japan.
authors.forename: Yuushi
authors.initials: Y
authors.lastname: Uchida
authors.forename: Hideki
authors.initials: H
authors.lastname: Shiba
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Komatsuzawa
authors.forename: Chikara
authors.initials: C
authors.lastname: Hirono
authors.forename: Arata
authors.initials: A
authors.lastname: Ashikaga
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Fujita
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kawaguchi
authors.forename: Motoyuki
authors.initials: M
authors.lastname: Sugai
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Shiba
authors.forename: Hidemi
authors.initials: H
authors.lastname: Kurihara
mesh_terms: D016976:Aggregatibacter actinomycetemcomitans / Q000276:immunology*; D001425:Bacterial Outer Membrane Proteins / Q000494:pharmacology*; D002450:Cell Communication / Q000187:drug effects / Q000276:immunology*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D017629:Gap Junctions / Q000187:drug effects / Q000276:immunology*; D005881:Gingiva / Q000187:drug effects / Q000276:immunology* / Q000382:microbiology*; D006801:Humans; D016209:Interleukin-8 / Q000276:immunology*; D014227:Triazines / Q000008:administration & dosage*
chemical_list: D001425:Bacterial Outer Membrane Proteins; D016209:Interleukin-8; C117494:Omp29 protein, Actinobacillus actinomycetemcomitans; D014227:Triazines; C041836:irsogladine