Allergic Inflammation Caused by Dimerized Translationally Controlled Tumor Protein is Attenuated by Cardamonin

Hyunsoo Cho,Haejun Pyun,Joo-Won Nam,Kyunglim Lee,Jiyoung Park,Eun Kyoung Seo

doi:10.3389/fphar.2021.765521

Hyunsoo Cho, Haejun Pyun + Show 4 more

Open Access

https://doi.org/10.3389/fphar.2021.765521

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Abstract

We demonstrated in our previous reports that dimeric form of translationally controlled tumor protein (dTCTP) initiates a variety of allergic phenomena. In the present study, we examined whether and how dTCTP’s role in allergic inflammation can be modulated or negated. The possible potential of cardamonin as an anti-allergic agent was assessed by ELISA using BEAS-2B cells and OVA-challenged allergic mouse model. The interaction between cardamonin and dTCTP was confirmed by SPR assay. Cardamonin was found to reduce the secretion of IL-8 caused by dTCTP in BEAS-2B cells by interacting with dTCTP. This interaction between dTCTP and cardamonin was confirmed through kinetic analysis (KD = 4.72 ± 0.07 μM). Also, cardamonin reduced the migration of various inflammatory cells in the bronchoalveolar lavage fluid (BALF), inhibited OVA specific IgE secretion and bronchial remodeling. In addition, cardamonin was observed to have an anti-allergic response by inhibiting the activity of NF-κB. Cardamonin exerts anti-allergic anti-inflammatory effect by inhibiting dTCTP, suggesting that it may be useful in the therapy of allergic diseases.

Highlights

Controlled tumor protein (TCTP), variously called histamine releasing factor (HRF), p21, p23, and fortilin, is involved in a variety of biological and pathological processes (Bommer and Thiele, 2004), the extracellular histamine release (MacDonald et al, 1995) and inducing the production of interleukins from basophils, mast cells, and eosinophils (MacDonald et al, 1995; Kawakami, 2014)
To assess the inhibitory effects of cardamonin and helichrysetin on the Dimerized Translationally controlled tumor protein (TCTP) (dTCTP)-induced secretion of IL-8 in BEAS-2B cells, we tested their dose-dependent effects on BEAS-2B cell viability (Figure 2A)
Neither substance showed toxicity at concentrations below 2 μg/ml. We examined their effect on IL-8 secretion caused by dTCTP in BEAS-2B cells using a concentration range, where no cytotoxicity was observed

Summary

Introduction

Controlled tumor protein (TCTP), variously called histamine releasing factor (HRF), p21, p23, and fortilin, is involved in a variety of biological and pathological processes (Bommer and Thiele, 2004), the extracellular histamine release (MacDonald et al, 1995) and inducing the production of interleukins from basophils, mast cells, and eosinophils (MacDonald et al, 1995; Kawakami, 2014). TCTP acts in the extracellular space to form dimers with cytokine-like activity (Kim et al, 2009). It has been known to play an important role in late phase allergic reactions (Kim et al, 2009) Based on these findings, we hypothesized that by regulating dTCTP, it is possible to suppress late phase allergic responses. We tested our hypothesis in BALB/c mouse models and screened natural product libraries and selected chemical compounds for their ability to inhibit dTCTP’s role in allergic reactions. Using this approach, we identified cardamonin, a chalcone as one with this ability

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