title: Irsogladine maleate regulates the inflammatory related genes in human gingival epithelial cells stimulated by Aggregatibacter actinomycetemcomitans.
abstract: Periodontitis is an infectious inflammatory disease. Our previous studies have revealed that irsogladine maleate (IM) regulates intercellular junctional function and chemokine secretion in gingival epithelium, resulting in the suppression of the onset of periodontal disease in a rat model. Therefore, it is plausible that IM is a promising preventive remedy for periodontal disease. In this study, to gain a better understanding of IM in gingival epithelial cells, we employed a DNA microarray analysis. More specifically, human gingival epithelial cells (HGEC) were exposed to Aggregatibacter actinomycetemcomitans (A. actinomycetemcomitans) in the presence or absence of IM. Then, a human genome focus array was used. A. actinomycetemcomitans facilitated the expression of several inflammatory-related genes, including these for matrix metalloproteinase (MMP)-3, interleukin (IL)-6, and intercellular adhesion molecule-1 (ICAM-1) in HGEC, while these mRNA levels were attenuated by IM treatment. Importantly, consistent with mRNA levels, immunoblotting, immunofluorescence staining and ELISA analysis indicated that IM also abrogated the A. actinomycetemcomitans-induced increase in MMP-3, IL-6, and ICAM-1 at the protein level. In addition, inhibition of the ERK or p38 MAP kinase signaling cascade, previously reported to be disturbed by IM treatment in HGEC, clearly blocked A. actinomycetemcomitans-induced MMP-3, IL-6, or ICAM-1 protein expression. Moreover, animal study revealed that IM-pretreatment inhibited the A. actinomycetemcomitans-induced increase of ICAM-1 in gingival junctional epithelium. Taken together, these results suggested that IM can regulate inflammatory responses in HGEC by inhibiting the ERK or p38 MAP kinase signaling cascade, which may result in suppression of inflammation in gingival tissue, thereby contributing to the prevention of periodontitis.
authors.affiliation: Department of Periodontal Medicine, Division of Applied Life Science, Hiroshima University Graduate School of Biomedical and Health Sciences, Japan.
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Miyagawa
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Fujita
authors.forename: Kazuhisa
authors.initials: K
authors.lastname: Ouhara
authors.forename: Shinji
authors.initials: S
authors.lastname: Matsuda
authors.forename: Mikihito
authors.initials: M
authors.lastname: Kajiya
authors.forename: Kouichi
authors.initials: K
authors.lastname: Hayashida
authors.forename: Haruka
authors.initials: H
authors.lastname: Imai
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Yoshimoto
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Iwata
authors.forename: Hideki
authors.initials: H
authors.lastname: Shiba
authors.forename: Yoshimitsu
authors.initials: Y
authors.lastname: Abiko
authors.forename: Hidemi
authors.initials: H
authors.lastname: Kurihara
mesh_terms: D000189:Actinobacillus Infections / Q000276:immunology*; D016976:Aggregatibacter actinomycetemcomitans / Q000276:immunology*; D000818:Animals; D000942:Antigens, Bacterial / Q000276:immunology; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000187:drug effects* / Q000473:pathology; D005786:Gene Expression Regulation / Q000187:drug effects*; D005881:Gingiva / Q000473:pathology*; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis; D010518:Periodontitis / Q000235:genetics / Q000382:microbiology / Q000517:prevention & control*; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects; D014227:Triazines / Q000494:pharmacology* / Q000627:therapeutic use; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D000942:Antigens, Bacterial; D014227:Triazines; D048051:p38 Mitogen-Activated Protein Kinases; C041836:irsogladine