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Targeting the translationally controlled tumor protein by a monoclonal antibody improves allergic airway inflammation in mice
- Title
- Targeting the translationally controlled tumor protein by a monoclonal antibody improves allergic airway inflammation in mice
- Authors
- Bae; Hae-Duck; Cho; Minyoung; Seo; Hyeran; Lyoo; In Kyoon; Lee; Kyunglim
- Ewha Authors
- 이경림; 류인균
- SCOPUS Author ID
- 이경림; 류인균
- Issue Date
- 2023
- Journal Title
- Biomedicine and Pharmacotherapy
- ISSN
- 0753-3322
- Citation
- Biomedicine and Pharmacotherapy vol. 168
- Keywords
- Airway inflammation; Antihistaminic drug; Histamine-releasing factor (HRF); Monoclonal antibody; Translationally controlled tumor protein (TCTP)
- Publisher
- Elsevier Masson s.r.l.
- Indexed
- SCIE; SCOPUS
- Document Type
- Article
- 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. Our results demonstrate that specific targeting of the flexible loop of TCTP is a potent strategy for treating airway inflammatory diseases. © 2023 The Authors
- DOI
- 10.1016/j.biopha.2023.115655
- Appears in Collections:
- 약학대학 > 약학과 > Journal papers
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