REFERENCE

논문 제목	Targeting the translationally controlled tumor protein by a monoclonal antibody improves allergic airway inflammation in mice
저자	Hae-Duck Bae, Minyoung Cho, Hyeran Seo, In Kyoon Lyoo, Kyunglim Lee
저널	Biomedicine & Pharmacotherapy
출판연도	2023
PMID	37806090
DOI	https://doi.org/10.1016/j.biopha.2023.115655

Abstract

Secretion of translationally controlled tumor protein (TCTP) was found in body fluids during the late phase of allergic reactions, implicating TCTP in allergic diseases. Furthermore, blocking TCTP has been shown to be helpful in treating asthma and allergies in animal models. The objectives of this study were to produce anti-TCTP monoclonal antibodies (mAbs), test their ability to inhibit the cytokine-like function of dimeric TCTP (dTCTP) in vitro and to assess their therapeutic effects in a murine model of ovalbumin (OVA)-induced airway inflammation. We first verified the inhibitory effects of 4 anti-TCTP mAbs on dTCTP-induced secretion of IL-8 in BEAS-2B cells. To investigate the anti-inflammatory effect of anti-TCTP mAbs on allergic airway inflammation, we treated OVA-sensitized mice with anti-TCTP mAbs before OVA challenge. The changes in bronchoalveolar lavage fluid (BALF) cells, IL-4, IL-5, and IL-13 levels in both BALF and lung homogenates, plasma levels of OVA-specific IgE, and lung tissues were analyzed. We found that JEW-M449 anti-TCTP mAb bound to the flexible loop of TCTP and significantly inhibited dTCTP-induced IL-8 release, making it the most effective inhibitor in our study. We also found that treatment with JEW-M449 significantly reduced the infiltration of inflammatory cells and suppressed the OVA-induced upregulation of type 2 cytokines in both BALF and lung homogenates in a dose-dependent manner. In addition, JEW-M449 significantly attenuated the degree of goblet cell hyperplasia and mucus secretion.

요약

TCTP(번역 조절 종양 단백질)는 알레르기 반응의 후기 단계에서 체액 내로 분비되어 천식 등 알레르기 질환에 관여하는 주요 염증 매개체로 알려져 있습니다. 이화여자대학교 연구팀은 TCTP의 이량체(dTCTP)가 나타내는 사이토카인 유사 활성을 억제하기 위해 항-TCTP 단클론항체(mAb)를 제작하고, 그 중 JEW-M449가 TCTP의 flexible loop 부위에 결합하여 IL-8 분비를 가장 효과적으로 억제함을 확인하였습니다. OVA로 감작된 마우스 모델에 JEW-M449를 투여한 결과, 기관지폐포세척액(BALF) 및 폐 조직 내 염증세포 침윤과 Th2 사이토카인(IL-4, IL-5, IL-13) 수치가 용량 의존적으로 유의하게 감소하였으며, 혈장 OVA 특이적 IgE 수준 및 배상세포 과형성·점액 분비도 현저히 억제되었습니다. 본 연구에서 항-TCTP 단클론항체 생산에 YntoAb의 Antibody service / ELI-lite package가 활용되었습니다.

Services used : Antibody service / ELI-lite package  👉 [서비스 바로가기]

 

논문 원문 보기 (PubMed)