Treatment with phosphodiester CpG-ODN ameliorates atopic dermatitis by enhancing TGF-β signaling.
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| Abstract |
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-��-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. [BMB Reports 2021; 54(2): 142-147].
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| Authors | Won-Kook Ham, Eun-Jung Lee, Myung Shin Jeon, Hae-Young Kim, Gaurav Agrahari, Eun-Joo An, Chul Hwan Bang, Doo-Sik Kim, Tae-Yoon Kim |
| Journal | BMB reports (BMB Rep) Vol. 54 Issue 2 Pg. 142-147 (Feb 2021) ISSN: 1976-670X [Electronic] Korea (South) |
| PMID | 33612150 (Publication Type: News) |
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