Irsogladine maleate counters the interleukin-1 beta-induced suppression in gap-junctional intercellular communication but does not affect the interleukin-1 beta-induced zonula occludens protein-1 levels in human gingival epithelial cells.
OBJECTIVE
Irsogladine maleate counters gap junctional intercellular communication reduction induced by interleukin-8 or Actinobacillus actinomycetemcomitans in cultured human gingival epithelial cells. Interleukin-1 beta is involved in periodontal disease. Little is known, however, about the effect of interleukin-1 beta on intercellular junctional complexes in human gingival epithelial cells. Furthermore, irsogladine maleate may affect the actions of interleukin-1 beta. In this study, we examined how interleukin-1 beta affected gap junctional intercellular communication, connexin 43 and zonula occludens protein-1, and how irsogladine maleate modulated the interleukin-1 beta-induced changes in the intercellular junctional complexes in human gingival epithelial cells.


METHODS
Human gingival epithelial cells were exposed to interleukin-1 beta, with or without irsogladine maleate. Connexin 43 and zonula occludens protein-1 were examined at mRNA and protein levels by real-time polymerase chain reaction and western blotting, respectively. Gap junctional intercellular communication was determined using the dye transfer method. The expression of zonula occludens protein-1 was also confirmed by immunofluorescence.


RESULTS
Interleukin-1 beta decreased connexin 43 mRNA levels, but increased zonula occludens protein-1 mRNA levels. Irsogladine maleate countered the interleukin-1 beta-induced reduction in gap junctional intercellular communication and connexin 43 levels. However, irsogladine maleate did not influence the increased zonula occludens protein-1 levels.


CONCLUSIONS
The effect of interleukin-1 beta on gap junctional intercellular communication and tight junctions of human gingival epithelial cells is different. The recovery of gap junctional intercellular communication by irsogladine maleate in the gingival epithelium may be a normal process in gingival epithelial homeostasis.
Fujita
T
T
Department of Periodontal Medicine, Division of Frontier Medical Science, Hiroshima University Graduate School of Biomedical Sciences, Hiroshima, Japan. tfuji@hiroshima-u.ac.jp
Ashikaga
A
A
Shiba
H
H
Kajiya
M
M
Kishimoto
A
A
Hirata
R
R
Tsunekuni
N
N
Hirono
C
C
Kawaguchi
H
H
Shiba
Y
Y
Kurihara
H
H
D000970:Antineoplastic Agents / Q000494:pharmacology*; D018031:Connexin 43 / Q000378:metabolism; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects*; D017629:Gap Junctions / Q000187:drug effects* / Q000378:metabolism; D005881:Gingiva / Q000166:cytology; D006801:Humans; D053583:Interleukin-1beta / Q000037:antagonists & inhibitors* / Q000378:metabolism / Q000494:pharmacology; D008565:Membrane Proteins / Q000378:metabolism*; D010750:Phosphoproteins / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D014227:Triazines / Q000494:pharmacology*; D062826:Zonula Occludens-1 Protein
D000970:Antineoplastic Agents; D018031:Connexin 43; D053583:Interleukin-1beta; D008565:Membrane Proteins; D010750:Phosphoproteins; D012333:RNA, Messenger; C569042:TJP1 protein, human; D014227:Triazines; D062826:Zonula Occludens-1 Protein; C041836:irsogladine