SUGAHARA Toshio Okayama University Graduate School of Medicine and Dentistry, Department of Oral and Maxillofacial Reconstructive Surgery, Professor, 大学院・医歯学総合研究科, 教授 (10116048)
YAMAAI Tomoichiro Okayama University Graduate School of Medicine and Dentistry, Department of Oral Function and Anatomy, Assistant, 大学院・医歯学総合研究科, 助手 (00158057)
The biophiraxic barriers against external stimuli, mechanical trauma and microbiological pathogens consist of the oral epithelia and inflammatory cells. Defensins are cationic antimicrobial peptides, which are categorized into two types, human α-defensins (HNPs) and human β-defensins (HBDs). HBD-2, which is produced by the keratinocytes of the skin, is known to be strongly up-regulated by bacterial infections, lipopolysaccharides (LPS), interleukin (IL)-1 alpha, IL-1 beta and TNF-alpha.
Interestingly, HBD-2 expression is observed not only in the inflamed lesions associated with bacterial infection but also in other non-inflamed lesions such as carcinomas. Furthermore, so-called proliferation death of normal epidermal cells line (NHEK) was shown to be induced by HBD-2 generated by a squamous cell carcinoma cell line in vitro.
We identified that this effect of cellular proliferation death, is similar to the effect of low-dose irradiation on cells. This may in turn, help the multiplication of squamous cell carcinoma cells, because HBD-2 had no direct effect on the survival of squamous cell carcinoma cells. We suggested that up regulation of HBD-2 might have side effects, unrelated to defense mechanisms, which would lead to the death of keratinocytes adjacent to the SCC which indirectly assists in the multiplication of tumor cells.
Also, defensin was up-regulated in host side by transplantation as a surgical injury. We reported that defensin induced Histamine release from Mast Cells. Histamine was known to induce inflammation. And a High concentration of defensin was suggested to cause injury to neighboring normal cells. The purpose of our study was to regulate the defensin expression and obtain a favorable healing of grafts.