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A novel sphingosylphosphorylcholine and sphingosine-1-phosphate receptor 1 antagonist, KRO-105714, for alleviating atopic dermatitis
DC Field | Value | Language |
---|---|---|
dc.contributor.author | Yoon, Sae-Bom | - |
dc.contributor.author | Lee, Chang Hoon | - |
dc.contributor.author | Kim, Hyun Young | - |
dc.contributor.author | Jeong, Daeyoung | - |
dc.contributor.author | Jeon, Moon Kook | - |
dc.contributor.author | Cho, Sun-A | - |
dc.contributor.author | Kim, Kwangmi | - |
dc.contributor.author | Lee, Taeho | - |
dc.contributor.author | Yang, Jung Y | - |
dc.contributor.author | Gong, Young-Dae | - |
dc.contributor.author | Cho, Heeyeong | - |
dc.date.accessioned | 2020-07-15T06:00:16Z | - |
dc.date.available | 2020-07-15T15:53:56Z | - |
dc.date.issued | 2020-05-29 | - |
dc.identifier.citation | Journal of Inflammation. 2020 May 29;17(1):20 | ko_KR |
dc.identifier.issn | 1476-9255 | - |
dc.identifier.uri | https://hdl.handle.net/10371/168593 | - |
dc.description.abstract | Background
Atopic dermatitis (eczema) is a type of inflammation of the skin, which presents with itchy, red, swollen, and cracked skin. The high global incidence of atopic dermatitis makes it one of the major skin diseases threatening public health. Sphingosylphosphorylcholine (SPC) and sphingosine-1-phosphate (S1P) act as pro-inflammatory mediators, as an angiogenesis factor and a mitogen in skin fibroblasts, respectively, both of which are important biological responses to atopic dermatitis. The SPC level is known to be elevated in atopic dermatitis, resulting from abnormal expression of sphingomyelin (SM) deacylase, accompanied by a deficiency in ceramide. Also, S1P and its receptor, sphingosine-1-phosphate receptor 1 (S1P1) are important targets in treating atopic dermatitis. Results In this study, we found a novel antagonist of SPC and S1P1, KRO-105714, by screening 10,000 compounds. To screen the compounds, we used an SPC-induced cell proliferation assay based on a high-throughput screening (HTS) system and a human S1P1 protein-based [35S]-GTPγS binding assay. In addition, we confirmed the inhibitory effects of KRO-105714 on atopic dermatitis through related cell-based assays, including a tube formation assay, a cell migration assay, and an ELISA assay on inflammatory cytokines. Finally, we confirmed that KRO-105714 alleviates atopic dermatitis symptoms in a series of mouse models. Conclusions Taken together, our data suggest that SPC and S1P1 antagonist KRO-105714 has the potential to alleviate atopic dermatitis. | ko_KR |
dc.description.sponsorship | This work was supported by a grant from the Korea Research Council for Industrial Science and Technology (KK-1933-20) to HC, under the industrial infrastructure program for fundamental technologies and Korea Institute for Advancement of Technology through the Inter-ER Cooperation Projects (R0002017) which are funded by the Ministry of Trade, Industry & Energy, Korea to YDG. | ko_KR |
dc.language.iso | en | ko_KR |
dc.publisher | BMC | ko_KR |
dc.subject | Sphingosylphosphorylcholine | - |
dc.subject | Sphingosine-1-phosphate receptor 1 | - |
dc.subject | Antagonist | - |
dc.subject | Anti-inflammatory | - |
dc.subject | Atopic dermatitis | - |
dc.subject | High-throughput screening | - |
dc.title | A novel sphingosylphosphorylcholine and sphingosine-1-phosphate receptor 1 antagonist, KRO-105714, for alleviating atopic dermatitis | ko_KR |
dc.type | Article | ko_KR |
dc.contributor.AlternativeAuthor | 윤새범 | - |
dc.contributor.AlternativeAuthor | 이창훈 | - |
dc.contributor.AlternativeAuthor | 김현영 | - |
dc.contributor.AlternativeAuthor | 정대영 | - |
dc.contributor.AlternativeAuthor | 전문국 | - |
dc.contributor.AlternativeAuthor | 조선아 | - |
dc.contributor.AlternativeAuthor | 김광미 | - |
dc.contributor.AlternativeAuthor | 이태호 | - |
dc.identifier.doi | 10.1186/s12950-020-00244-6 | - |
dc.citation.journaltitle | Journal of Inflammation | ko_KR |
dc.language.rfc3066 | en | - |
dc.rights.holder | The Author(s) | - |
dc.date.updated | 2020-06-16T09:35:21Z | - |
dc.citation.number | 1 | ko_KR |
dc.citation.startpage | 20 | ko_KR |
dc.citation.volume | 17 | ko_KR |
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