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二氢卟吩e6介导的光动力疗法通过NFκB和丝裂原活化蛋白激酶信号通路抑制痤疮丙酸杆菌诱导的炎症反应。

Chlorin e6-Mediated Photodynamic Therapy Suppresses P. acnes-Induced Inflammatory Response via NFκB and MAPKs Signaling Pathway.

作者信息

Wang Yoon-Young, Ryu A-Reum, Jin Solee, Jeon Yu-Mi, Lee Mi-Young

机构信息

Department of Medical Science, College of Medical Sciences, Soonchunhyang University, Asan, Chungnam, Republic of Korea.

Korea Brain Research Institute, Research Division, Daegu, Republic of Korea.

出版信息

PLoS One. 2017 Jan 24;12(1):e0170599. doi: 10.1371/journal.pone.0170599. eCollection 2017.

Abstract

Photodynamic therapy (PDT), consisting of photosensitizer, light, and oxygen has been used for the treatment of various diseases including cancers, microbial infections and skin disorders. In this study, we examined the anti-inflammatory effect of chlorin e6-mediated PDT in P. acnes-infected HaCaT cells using photosensitizer chlorin e6 (Ce6) and halogen light. The live and heat-killed P. acnes triggered an upregulation of inflammatory molecules such as iNOS, NO, and inflammatory cytokine in HaCaT cells and mouse model. Ce6-mediated PDT notably downregulated the expression of these inflammatory molecules in vitro and in vivo. Similarly, chlorin e6-mediated PDT was capable of regulating inflammatory response in both live and heat killed S. epidermidis exposed HaCaT cells. Moreover, phosphorylation of p38, JNK, and ERK were reduced by Ce6-mediated PDT. Ce6-mediated PDT also reduced the phosphorylation of IKKα/β, IĸBα and NFκB p65 in P. acnes-stimulated HaCaT cells. In addition, the dramatic increase in the nuclear translocation of NFκB p65 observed upon stimulation with P. acnes was markedly impaired by Ce6-based PDT. This is the first suggestion that Ce6-mediated PDT suppresses P. acnes-induced inflammation through modulating NFκB and MAPKs signaling pathways.

摘要

光动力疗法(PDT)由光敏剂、光和氧气组成,已被用于治疗包括癌症、微生物感染和皮肤疾病在内的各种疾病。在本研究中,我们使用光敏剂二氢卟吩e6(Ce6)和卤素光,研究了二氢卟吩e6介导的光动力疗法对痤疮丙酸杆菌感染的HaCaT细胞的抗炎作用。活的和热灭活的痤疮丙酸杆菌在HaCaT细胞和小鼠模型中引发了炎症分子如诱导型一氧化氮合酶(iNOS)、一氧化氮(NO)和炎性细胞因子的上调。Ce6介导的光动力疗法在体外和体内均显著下调了这些炎症分子的表达。同样,二氢卟吩e6介导的光动力疗法能够调节活的和热灭活的表皮葡萄球菌暴露的HaCaT细胞中的炎症反应。此外,Ce6介导的光动力疗法降低了p38、JNK和ERK的磷酸化。Ce6介导的光动力疗法还降低了痤疮丙酸杆菌刺激的HaCaT细胞中IKKα/β、IκBα和NFκB p65的磷酸化。此外,在痤疮丙酸杆菌刺激下观察到的NFκB p65核转位的显著增加被基于Ce6的光动力疗法显著削弱。这首次表明Ce6介导的光动力疗法通过调节NFκB和丝裂原活化蛋白激酶(MAPKs)信号通路来抑制痤疮丙酸杆菌诱导的炎症。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6d74/5261614/5972044af91b/pone.0170599.g001.jpg

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