Irsogladine maleate regulates neutrophil migration and E-cadherin expression in gingival epithelium stimulated by Aggregatibacter actinomycetemcomitans

Fujita Tsuyoshi

Kishimoto Akiyoshi

Shiba Hideki

Hayashida Kouichi

Kajiya Mikihito

Uchida Yuushi

Matsuda Shinji

Takeda Katsuhiro

Ouhara Kazuhisa

Kawaguchi Hiroyuki

Abiko Yoshimitsu

Kurihara Hidemi

Biochemical pharmacology

Irsogladine maleate (IM) counters Aggregatibacter actinomycetemcomitans-induced reduction of the gap junction intercellular communication and the expression of zonula occludens-1, which is a major tight junction structured protein, in cultured human gingival epithelial cells (HGEC). In addition, IM obviates the A. actinomycetemcomitans-induced increase in interleukin (IL)-8 levels in HGEC. Thus, by regulating the intercellular junctional complex and chemokine secretion in HGEC, IM may be useful to prevent periodontal disease. To clarify the effects and regulatory mechanism of IM in vivo and in vitro, we examined the expression of E-cadherin and neutrophil chemotaxis induced by A. actinomycetemcomitans under IM pretreatment. Immunohistochemical studies revealed that A. actinomycetemcomitans application to the gingival sulcus decreased the number of cells positive for E-cadherin and increased those positive for cytokine-induced neutrophil chemoattractant-2α (CINC-2α) in rat gingival epithelium.

However, in IM-pretreated rats, A. actinomycetemcomitans application had little effect on CINC-2α and E-cadherin in gingival epithelium. In cultured HGEC, real-time PCR and Western blotting showed that IM and the ERK inhibitor PD98059 abolished the A. actinomycetemcomitans-induced increase in CXCL-1 and IL-8 in HGEC. On the other hand, IM, PD98059, and the p38 MAP kinase inhibitor SB203580 recovered the decrease in E-cadherin expression. In addition, conditioned medium from A. actinomycetemcomitans-stimulated HGEC enhanced human neutrophil chemotaxis, compared to that from un-stimulated HGEC or that from A. actinomycetemcomitans-stimulated HGEC under IM pretreatment. Furthermore, IM down-regulated the p38 MAP kinase and ERK phosphorylations induced by A. actinomycetemcomitans. In conclusion, IM may control A. actinomycetemcomitans-induced gingival inflammation by regulating neutrophil migration and E-cadherin expression in gingival epithelium.

Irsogladine maleate

Aggregatibacter actinomycetemcomitans

E-cadherin

Neutrophil migration

CXC-chemokine

Gingival epithelial cells

Medical sciences [ 490 ]

eng

Elsevier

Copyright (c) 2010 Elsevier Inc.

[NCID] AA00564486

[ISSN] 0006-2952

[DOI] 10.1016/j.bcp.2010.01.017

[DOI] http://dx.doi.org/10.1016/j.bcp.2010.01.017 isVersionOf