PEPT1 ENHANCED BACTERIAL PEPTIDE TRANSPORT INTO LNFLAMED COLONIC EPITHELIUM AND INDUCES NEUTROPHIL RECRUITMENT

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K09398
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: National Defense Medical College
• Principal Investigator: WATANABE CHIKAKO 防衛医科大学校(医学教育部医学科進学課程及び専門課程、動物実験施設、共同利用研究施設、病院並びに防衛, 内科学, 講師 (90365263)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: ペプチド / 輸送体

Outline of Final Research Achievements

Peptide transporter (PEPT) 1, a transporter responsible for peptide absorption, is mainly expressed in the small intestine. Recently it has been reported the expression is upregulated in the inflamed colon, possibly contributing to the development of inflammatory bowel disease by transporting bacterial or food dericed peptides. However, there is no direct evidence how PEPT1 is involved in neutrophil recruitment to colonic microcirculation in the inflamed colon.The aim of this study is to investigate the dynamic process in vivo how PEPT1-mediated bacterial derived peptide transport affects neutrophil trafficking in the inflamed murine colonic mucosa.
PEPT1 expression in the inflamed colonic epithelium facilitated bacterial derived peptide uptake, and dramatically enhanced neutrophil trafficking to the colonic mucosa, in which IL1β and NLRP3 were possibly involved.

Free Research Field

腸管免疫

Academic Significance and Societal Importance of the Research Achievements

腸炎において、腸管内腔の炎症の原因物質（細胞分解産物など）を腸上皮細胞内に取り込む細胞内ルートの門戸を制御することは、腸炎の新規治療のターゲット候補と成り得る。今回は炎症時にのみ大腸の粘膜上皮細胞に発現するペプチド輸送体に着目し、これが細胞内ルートの門戸である可能性についてin vivo観察し、さらに好中球遊走に関与していることから、ペプチド輸送体が腸管炎症の病態に関与していることを示した。