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KMID : 0624620210540020142
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BMB Reports
2021 Volume.54 No. 2 p.142 ~ p.147
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Treatment with phosphodiester CpG-ODN ameliorates atopic dermatitis by enhancing TGF-β signaling
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Ham Won-Kook
Lee Eun-Jung
Jeon Myung-Shin
Kim Hae-Young
Agrahari Gaurav
An Eun-Joo
Bang Chul-Hwan
Kim Doo-Sik
Kim Tae-Yoon
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Abstract
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Synthetic oligodeoxynucleotides (ODNs) containing unmethylated CpG phosphorothioate (PS CpG-ODN) are known to decrease IgE synthesis in Th2 allergy responses. Nonetheless, the therapeutic role of PS CpG-ODN is limited due to cytotoxicity. Therefore, we developed a phosphodiester (PO) form of CpG-ODN (46O) with reduced toxicity but effective against allergies. In this study, we first compared the toxicity of 46O with CpG-ODNs containing a PS backbone (1826S). We also investigated the therapeutic efficacy and mechanism of 46O injected intravenously in a mouse model of ovalbumin (OVA)- induced atopic dermatitis (AD). To elucidate the mechanism of 46O underlying the inhibition of IgE production, IgE- and TGF-β-associated molecules were evaluated in CD40/IL-4- or LPS/IL-4-stimulated B cells. Our data showed that the treatment with 46O was associated with a lower hematological toxicity compared with 1826S. In addition, injection with 46O reduced erythema, epidermal thickness, and suppressed IgE and IL-4 synthesis in mice with OVA-induced AD. Additionally, 46O induced TGF-β production in LPS/IL-4-stimulated B cells via inhibition of Smad7, which suppressed IgE synthesis via interaction between Id2 and E2A. These findings suggest that enhanced TGF-β signaling is an effective treatment for IgE-mediated allergic conditions, and 46O may be safe and effective for treating allergic diseases such as AD and asthma.
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KEYWORD
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Atopic dermatitis, Id2/E2A interaction, IgE, Phosphodiester CpG-ODN, TGF-β, Smad7
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