Daphnetin inhibits proliferation and inflammatory response in human HaCaT keratinocytes and ameliorates imiquimod-induced psoriasis-like skin lesion in mice.
Daphnetin inhibits proliferation and inflammatory response in human HaCaT keratinocytes and ameliorates imiquimod-induced psoriasis-like skin lesion in mice.
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瑞香素抑制人 HaCaT 角质形成细胞的增殖和炎症反应，并改善咪喹莫特诱导的小鼠牛皮癣样皮肤病变
DOI：
10.1186/s40659-020-00316-0
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发表时间：
2020-10-20
影响因子：
6.7
通讯作者：
Yang M
中科院分区：
文献类型：
--
作者：
Gao J;Chen F;Fang H;Mi J;Qi Q;Yang M
GAO，Jintao等. Daphnetin inhibits proliferation and inflammatory response in human HaCaT keratinocytes and ameliorates imiquimod-induced psoriasis-like skin lesion in mice.生物研究[联机]。2020年，第53卷，第48页。电子版2020年11月9日。ISSN 0716-9760。http：//dx. doi。研究背景银屑病是一种常见的慢性炎症性皮肤病。角质形成细胞过度增殖和过度的炎症反应参与银屑病的发病机制。能够减弱角质形成细胞过度增殖和过度炎症反应的药物被认为对银屑病治疗有潜在的用途。瑞香素具有广泛的生物活性，包括抗增殖和抗炎。方法：采用IL-17 A、IL-22、制瘤素M、IL-1α和TNF-α（M5）混合物刺激HaCaT角质形成细胞，建立体外银屑病角质形成细胞模型。使用细胞计数试剂盒-8（CCK-8）测量细胞活力。采用实时定量PCR（qRT-PCR）检测过度增殖标记基因角蛋白6（KRT 6）、分化标记基因角蛋白1（KRT 1）和炎症因子IL-1β、IL-6、IL-8、TNF-α、IL-23 A和MCP-1的mRNA水平。Western blotting检测p65和p-p65蛋白表达水平。间接免疫荧光法（IFA）检测p65核转位。采用咪喹莫特（Imiquimod，IMQ）建立银屑病样小鼠模型。根据银屑病面积严重程度指数（PASI）对银屑病严重程度（红斑、鳞屑）进行评分。苏木精-伊红（H&E）染色观察皮损组织学变化。采用qRT-PCR方法检测皮损中炎症因子IL-6、TNF-α、IL-23 A和IL-17 A的表达。M5刺激显著上调IL-1β、IL-6、IL-8、TNF-α、IL-23 A和MCP-1的mRNA水平。然而，瑞香素治疗部分减弱了这些炎性细胞因子的上调。发现瑞香素能够抑制HaCaT角质形成细胞中的p65磷酸化和核转位。此外，瑞香素显著改善IMQ诱导的银屑病样小鼠模型的皮肤病变的严重程度（红斑、鳞屑和表皮厚度、炎性细胞浸润）。结论：瑞香素可通过抑制NF-κB信号通路抑制M5诱导的HaCaT角质形成细胞增殖和炎症反应。瑞香素能改善IMQ诱导的银屑病样小鼠模型的皮损严重程度和炎症状态。瑞香素可能是一个有吸引力的候选人，为未来的发展，作为一种抗银屑病剂。
GAO, Jintao et al. Daphnetin inhibits proliferation and inflammatory response in human HaCaT keratinocytes and ameliorates imiquimod-induced psoriasis-like skin lesion in mice. Biol. Res.[online]. 2020, vol. 53, 48. Epub 09-Nov-2020. ISSN 0716-9760. http://dx. doi. org/10.1186/s40659-020-00316-0.Background:Psoriasis is a common chronic inflammatory skin disease. Keratinocytes hyperproliferation and excessive inflammatory response contribute to psoriasis pathogenesis. The agents able to attenuate keratinocytes hyper-proliferation and excessive inflammatory response are considered to be potentially useful for psoriasis treatment. Daphnetin exhibits broad bioactivities including anti-proliferation and anti-inflammatory. This study aims to evaluate the anti-psoriatic potential of daphnetin in vitro and in vivo, and explore underlying mechanisms.Methods:HaCaT keratinocytes was stimulated with the mixture of IL-17A, IL-22, oncostatin M, IL-1α, and TNF-α (M5) to establish psoriatic keratinocyte model in vitro. Cell viability was measured using Cell Counting Kit-8 (CCK-8). Quantitative Real-Time PCR (qRT-PCR) was performed to measure the mRNA levels of hyperproliferative marker gene keratin 6 (KRT6), differentiation marker gene keratin 1 (KRT1) and inflammatory factors IL-1β, IL-6, IL-8, TNF-α, IL-23A and MCP-1. Western blotting was used to detect the protein levels of p65 and p-p65. Indirect immunofluorescence assay (IFA) was carried out to detect p65 nuclear translocation. Imiquimod (IMQ) was used to construct psoriasis-like mouse model. Psoriasis severity (erythema, scaling) was scored based on Psoriasis Area Severity Index (PASI). Hematoxylin and eosin (H&E) staining was performed to examine histological change in skin lesion. The expression of inflammatory factors including IL-6, TNF-α, IL-23A and IL-17A in skin lesion was measured by qRT-PCR.Results:Daphnetin attenuated M5-induced hyperproliferation in HaCaT keratinocytes. M5 stimulation significantly upregulated mRNA levels of IL-1β, IL-6, IL-8, TNF-α, IL-23A and MCP-1. However, daphnetin treatment partially attenuated the upregulation of those inflammatory cytokines. Daphnetin was found to be able to inhibit p65 phosphorylation and nuclear translocation in HaCaT keratinocytes. In addition, daphnetin significantly ameliorate the severity of skin lesion (erythema, scaling and epidermal thickness, inflammatory cell infiltration) in IMQ-induced psoriasis-like mouse model. Daphnetin treatment attenuated IMQ-induced upregulation of inflammatory cytokines including IL-6, IL-23A and IL-17A in skin lesion of mice.Conclusions:Daphnetin was able to attenuate proliferation and inflammatory response induced by M5 in HaCaT keratinocytes through suppression of NF-κB signaling pathway. Daphnetin could ameliorate the severity of skin lesion and improve inflammation status in IMQ-induced psoriasis-like mouse model. Daphnetin could be an attractive candidate for future development as an anti-psoriatic agent.
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影响因子：
7.5
作者：
Kumar, Abhishek;Jha, S.;Pattanayak, Shakti P.
通讯作者：
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影响因子：
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DOI：
10.1038/nrdp.2016.82
发表时间：
2016-11-24
期刊：
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Bowman EP
DOI：
10.1016/j.jaci.2017.07.004
发表时间：
2017-09
期刊：
The Journal of allergy and clinical immunology
影响因子：
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通讯作者：
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