Nucleic acid recognition in oral mucosa and investigation of novel regulatory mechanism of antimicrobial peptides

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K11840
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Surgical dentistry
• Research Institution: Hiroshima University
• Principal Investigator: Ohta Kouji 広島大学, 医系科学研究科(歯), 教授 (20335681)
• Co-Investigator(Kenkyū-buntansha): 武知 正晃 広島大学, 医系科学研究科(歯), 准教授 (00304535) ; 重石 英生 広島大学, 医系科学研究科(歯), 講師 (90397943)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: 核酸認識機構 / 口腔粘膜上皮細胞 / 抗菌ペプチド / 口腔粘膜炎症性疾患

Outline of Final Research Achievements

The mechanism of nucleic acid recognition in oral mucosa is unknown. On the other hand, the antimicrobial peptide LL-37 is detected in epithelial inflammatory diseases. However, it is well unknown whether LL-37 is associated with inflammatory responses induced by nucleic acid, in oral mucosa. Therefore, we examined the effect of LL-37 on nucleic acid-mediated inflammatory responses in immortalized human oral keratinocytes (RT7). From those results, LL-37 dramatically increased self and non-self nucleotides-mediated CXCL10 expression in RT7, and those inductions were associated with NF-κB signaling activation. We found that LL-37 enables those nucleic acids to translocate into cytoplasm. In conclusion, LL-37 promotes exogenous nucleic acids-mediated inflammatory responses in oral keratinocytes, and that may be involved in the development of oral mucosal inflammatory diseases.

Free Research Field

外科系歯学

Academic Significance and Societal Importance of the Research Achievements

今回の研究によって口腔粘膜細胞が, 自己DNAや非自己DNAと結合し，T細胞活性化因子などの炎症性遺伝子の発現誘導を行っていること，また唾液など工区に存在する抗菌ペプチドLL-37 がそれらの自己，非自己DNAを口腔粘膜上皮細胞内に導入し，核酸で誘導される免疫応答を調節している可能性を明らかにした。今回の研究成果は，口腔粘膜の新規免疫応答機構を解明するだけでなく，口腔粘膜炎症性疾患に対する新たな治療や，検査法への開発につながることが期待できると考えている。