The development a new treatment for Palmoplantar pustulosis with improving the abnormal antimicrobial peptide expression

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K10128
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Dermatology
• Research Institution: Ehime University
• Principal Investigator: murakami masamoto 愛媛大学, 医学系研究科, 准教授 (20278302)
• Research Collaborator: Tsuda Teruko ; Tan Eriko ; Kameda Kenji
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: 掌蹠膿疱症 / 抗菌ペプチド / hCAP-18 / TLN-58

Outline of Final Research Achievements

The abnormal fragment of hCAP-18 in PPP vesicle was searched with several experiments, and TLN-58 was confirmed. The responsible proteinase was searched with MASCOT database, and neutrophilic elastase was found in the database. As a proteinase inhibitor for it, alpha one antitrypsin was selected and tested if it could suppress the protein processing of hCAP-18 to TLN-58, and we could confirm the prevention of processing. TLN-58 synthetic peptide induces the inflammatory response in primary keratinocyte culture and LSE, but not in sweat gland cells (NCL-SG3), especially for IL-8, comparing with LL-37. In the mouse model, the peptide could induce inflammatory changes in skin tissue, too. However, the proteinase inhibitor induced inflammatory response as an irritant, so that we failed to establish it as a new treatment for PPP.

Free Research Field

皮膚科学

Academic Significance and Societal Importance of the Research Achievements

掌蹠膿疱症の病態に関わる因子がまた新たに一つ同定された。水疱内容における異常な抗菌ペプチドの発現様式が本疾患の病態に関わることが明らかとなり、将来の治療オプションを考える上で、重要な発見となった。