Irsogladine Maleate inhibits S100 protein expression in Gingival Epithelial cells

Objective:

S100 proteins are calcium binding proteins, and the expressions are induced by inflammatory molecules, such as lipopolysaccharide and interleukin-1β in gingival epithelial cells. Periodontal ligament cells, neutrophils and monocytes express S100 proteins in inflamed periodontal lesion. Thus, S100 proteins are thought to play an important role in initial stage of periodontal inflammation. We have reported that Irsogladine maleate (IM) obviates the increase in interleukin-8 (IL-8) induced by Aggregatibacter actinomycetemcomitans (A. actinomycetemcomitans) in human gingival epithelial cells (HGEC), and IM may eliminate initial perturbation of gingival epithelial cells by regulating IL-8 production after periodontal pathogen exposure. A major question is whether S100 proteins can be regulated by A. actinomycetemcomitans and IM in HGEC. In the present study, we investigated the mRNA expression of S100 proteins in HGEC and the effects of A. actinomycetemcomitans and IM on S100 productions.

Methods:

HGEC were prepared from healthy gingival tissues obtained from subjects in a protocol approved by the Ethics Committee of the Hiroshima University. HGEC exposed to A. actinomycetemcomitans were cultured in the presence or absence of IM. The mRNA expressions of S100 proteins (S100-B, -P, -A1, -A3, -A7, -A8, -A9, -A12 and -A13) were examined by RT-PCR.

Results:

HGEC expressed the mRNA of S100P, -A1, -A3, A7, -A8, -A9, -A12 and -A13. A. actinomycetemcomitans stimulated the mRNA expression of S100-P and S100-A7 in HGEC. IM inhibited the increased levels of S100A7 mRNA in HGEC exposed to A. actinomycetemcomitans.

Conclusions:

The present study has demonstrated that various S100 proteins are expressed in gingival epithelial cells and that S100P and S100A7 were upragulated by A. actinomycetemcomitans. Furthermore, IM, modulating inflammatory responses of S100 proteins as well as IL-8 in gingival epithelial cells, may suppress periodontal inflammation.