2005 Fiscal Year Final Research Report Summary
Elucidation of the regulatory mechanism of calprotectin expression in oral epithelial cells and basic study of application for periodontal therapy
| Project/Area Number |
15592190
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Periodontal dentistry
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| Research Institution | The University of Tokushima |
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Principal Investigator |
ASANO Masahiro The University of Tokushima, Medical・Dental Hospital, Research assistant, 医学部・歯学部附属病院, 助手 (30335822)
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| Co-Investigator(Kenkyū-buntansha) |
KATAOKA Masatoshi The University of Tokushima, Institute for Genome Research, Associate Professor, ゲノム機能研究センター, 助教授 (20224438)
KIDO Jun-ichi The University of Tokushima, Institute of Health Biosciences, Associate Professor, 大学院・ヘルスバイオサイエンス研究部, 助教授 (10195315)
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| Project Period (FY) |
2003 – 2005
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| Keywords | Calprotectin / Antimicrobial peptide / Epithelial cells / Differentiation regulatory factors / Periodontal diseases / Immunotherapy |
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| Research Abstract |
Calprotectin (S100A8/S100A9) is an antimicrobial peptide which is produced by epithelial cells, and inhibits the growth of periodontophatic bacteria and adhesion of bacteria to epithelium. Calprotectin plays an important role in periodontal immunity, but the regulatory mechanism of calprotectin expression is not well known. In the present study, I investigated the factors which regulated calprotectin expression in human gingival keratinocytes and its regulatory mechanism. IL-1α and calcium, the up-regulators of keratinocyte differentiation, significantly increased mRNA expression of S100A8/S100A9 and calprotectin protein. On the other hand, TGF-β, the down-regulator of differentiation, clearly decreased the expression of calprotectin genes and protein. Furthermore, retinoic acid, the down-regulator of differentiation, suppressed the IL-1α-induced calprotectin expression. I prepared the deletion constructs containing promoter region of S100A8 or S100A9 gene and investigated the mechanism by luciferase assay. I found the decrease of luciferase activity in -765/-722 and -256/-111 regions of S100A8 deletion constructs, and in -188/-53 region of S100A9 deletion constructs. These region of two genes contained the DNA binding site to C/EBP, transcriptional factor. I showed the increase of C/EBP DNA binding activity in gingival keratinocytes stimulated by calcium and Il-1α. Taken together, calprotectin expression in gingival keratinocytes is regulated by the factors which affect keratinocyte differentiation and their regulation is related to C/EBP. I think that the elucidation of calprotectin expression in gingival keratinocytes plays a role in the development of periodontal immunotherapy using antimicrobial peptides.
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