Development of new treatments for indigenous skin flora and intractable skin ulcers caused by HMGB1 A-BOX

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K09485
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 56070:Plastic and reconstructive surgery-related
• Research Institution: Ehime University
• Principal Investigator: Mori Hideki 愛媛大学, 医学系研究科, 講師 (60325389)
• Co-Investigator(Kenkyū-buntansha): 村上 正基 愛媛大学, 医学系研究科, 准教授 (20278302)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: HMGB1 / 難治性皮膚潰瘍

Outline of Final Research Achievements

For intractable skin ulcers, we tried to develop a new treatment method that simultaneously aims at antibacterial and anti-inflammatory effects by using anti-HMGB1 antibody as a supplement, in addition to competitive bacteriostatic action by skin flora (Staphylococcus epidermidis). It showed an anti-inflammatory effect on monolayer cultured cells of human keratinocytes, but could not obtain the expected anti-inflammatory effect on subcutaneous abscesses in mice. The cause may be that TLR4 was not expressed in the human normal keratinized cells that we used this time, but that TLR4 and TLR not found in humans reacted in mice, limiting the anti-inflammatory effect.

Free Research Field

創傷治癒

Academic Significance and Societal Importance of the Research Achievements

創傷遅延の原因の一つに、創部での持続する病原性細菌感染とそれに伴う炎症反応の持続が挙げられる。通常は抗菌物質の全身投与が行われるが、そもそも遷延性難治性潰瘍周囲は瘢痕形成などにより血流が悪く、血液中の抗生物質の到達効率が著明に低下している。また、局所的な抗菌物質投与は耐性菌の早期出現を促すため、消毒剤や殺菌性外用剤が用いられることが多いが、これらは同時に細胞毒性を有するため、細胞毒性による創傷遅延を生ずる要因となっている
今回我々が提案する新規治療法は、細胞障害性を有さず、従来の抗菌物質投与と併用可能
な新たな治療オプションとしても期待される。