Oroxylin A attenuates psoriasiform skin inflammation by direct targeting p62 (sequestosome 1) via suppressing M1 macrophage polarization
文献类型：期刊论文
| 作者 | Ma, Yuxiang6,7; Liu, Yunyao5,7; Zhong, You4; Li, Xiangzheng7; Xu, Yujiao7; Chen, Leyi7; Gong, Litong3; Huang, He2; Chen, Xu1,5; He, Yuan7 |
| 刊名 | BRITISH JOURNAL OF PHARMACOLOGY
 |
| 出版日期 | 2024-09-23 |
| 页码 | 23 |
| 关键词 | autophagy macrophage polarization NF-kappa B oroxylin A sequestosome 1/p62 |
| ISSN号 | 0007-1188 |
| DOI | 10.1111/bph.17349 |
| 通讯作者 | Chen, Xu(chenx@pumcderm.cams.cn) ; He, Yuan(yuanhe0822@cpu.edu.cn) ; Qiang, Lei(lqiang@cpu.edu.cn) |
| 英文摘要 | Background and Purpose: Psoriasis results from the interplay of innate and adaptiveimmunity in the skin. Oroxylin A (OA) has shown anti-inflammatory effects in variousdisorders. This study explores oroxylin A potential in treating psoriasis, particularly itsimpact on type I macrophage (M phi 1) polarization. Experimental Approach: Oroxylin A-mediated therapeutic effects were evaluatedusing imiquimod-induced or IL-23-injected psoriatic mice models, followed by prote-omics assays to predict potential signalling and targeting proteins. Immunofluores-cence and immunoblot assays verified that oroxylin A suppresses NF-kB signalling inM1 macrophages. Co-immunoprecipitation and microscale thermophoresis (MST)assays further demonstrated that p62 (sequestosome 1) is the target protein fororoxylin A in macrophages. Oroxylin A-p62-mediated suppression of psoriasis wasvalidated in an imiquimod-induced p62 conditional knockout (cKO) mice model. Key Results: Oroxylin A demonstrated therapeutic efficacy in murine models inducedby imiquimod or IL-23 by attenuating cutaneous inflammation and mitigating M phi 1polarization via NF-kappa B signalling. Proteomics analysis suggested SQSTM1/p62 as akey target, confirmed to interact directly with oroxylin A. Oroxylin A disrupted thep62-PKC zeta interaction by binding to PB1 domain of p62. Its anti-inflammatory effectswere significantly reduced in macrophages from p62 cKO mice compared to thewild-type (WT) mice in psoriasis model, supporting oroxylin A role in suppressingM phi 1 polarization through its interaction with p62. Conclusion and Implications: Our findings demonstrated oroxylin A suppressed psor-iasiform skin inflammation in mouse models by blocking the PKC zeta-p62 interaction,subsequently inhibiting the activation of NF-kappa B p65 phosphorylation inmacrophages. |
| WOS关键词 | NF-KAPPA-B ; SEVERE PLAQUE PSORIASIS ; DOUBLE-BLIND ; IMPROVES PSORIASIS ; DENDRITIC CELLS ; ATYPICAL PKCS ; CONCISE GUIDE ; PROTEIN P62 ; ACTIVATION ; NEUTROPHILS |
| 资助项目 | Basic Ability Enhancement Program for Young and Middle-aged Teachers of Guilin Medical University[2022KY0513] ; Natural Science Foundation of Jiangsu Province[BK20211578] ; Natural Science Foundation of Jiangsu Province[BK20210419] ; Special Fund for Talents of Guangxi[AD220359310] ; National Natural Science Foundation of China[81974425] ; National Natural Science Foundation of China[82002907] ; National Natural Science Foundation of China[82360718] |
| WOS研究方向 | Pharmacology & Pharmacy |
| 语种 | 英语 |
| WOS记录号 | WOS:001318882700001 |
| 出版者 | WILEY |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/313430]  |
| 专题 | 中国科学院上海药物研究所 |
| 通讯作者 | Chen, Xu; He, Yuan; Qiang, Lei |
| 作者单位 | 1.Chinese Acad Med Sci, Key Lab Basic & Translat Res Immune Mediated Skin, Nanjing, Peoples R China 2.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Chem Biol, Shanghai 201203, Peoples R China 3.Jiangsu Chia Tai Tianqing Pharmaceut Co Ltd, Nanjing, Peoples R China 4.Zhuhai United Labs Co Ltd, Zhuhai, Guangdong, Peoples R China 5.Chinese Acad Med Sci & Peking Union Med Coll, Inst Dermatol, Jiangsu Key Lab Mol Biol Skin Dis & STIs, Nanjing 210042, Peoples R China 6.Guilin Med Univ, Dept Pharmacol, Guilin, Peoples R China 7.China Pharmaceut Univ, Sch Basic Med & Clin Pharm, State Key Lab Nat Med, Nanjing 211198, Peoples R China |
| 推荐引用方式 GB/T 7714 | Ma, Yuxiang,Liu, Yunyao,Zhong, You,et al. Oroxylin A attenuates psoriasiform skin inflammation by direct targeting p62 (sequestosome 1) via suppressing M1 macrophage polarization[J]. BRITISH JOURNAL OF PHARMACOLOGY,2024:23. |
| APA | Ma, Yuxiang.,Liu, Yunyao.,Zhong, You.,Li, Xiangzheng.,Xu, Yujiao.,...&Qiang, Lei.(2024).Oroxylin A attenuates psoriasiform skin inflammation by direct targeting p62 (sequestosome 1) via suppressing M1 macrophage polarization.BRITISH JOURNAL OF PHARMACOLOGY,23. |
| MLA | Ma, Yuxiang,et al."Oroxylin A attenuates psoriasiform skin inflammation by direct targeting p62 (sequestosome 1) via suppressing M1 macrophage polarization".BRITISH JOURNAL OF PHARMACOLOGY (2024):23. |
入库方式： OAI收割
来源：上海药物研究所
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