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痤疮丙酸杆菌 CAMP 因子靶向性痤疮疫苗的抗炎活性。

The Anti-Inflammatory Activities of Propionibacterium acnes CAMP Factor-Targeted Acne Vaccines.

机构信息

Department of Dermatology, School of Medicine, University of California, San Diego, California, USA.

Department of Biomedical Sciences and Engineering, National Central University, Jhongli, Taiwan.

出版信息

J Invest Dermatol. 2018 Nov;138(11):2355-2364. doi: 10.1016/j.jid.2018.05.032. Epub 2018 Jun 30.

Abstract

Inflammatory acne vulgaris afflicts hundreds of millions of people globally. Propionibacterium acnes, an opportunistic skin bacterium, has been linked to the pathogenesis of acne vulgaris. Our results show that a secretory Christie-Atkins-Munch-Petersen (CAMP) factor of P. acnes is up-regulated in anaerobic cultures. Mutation of CAMP factor significantly diminishes P. acnes colonization and inflammation in mice, demonstrating the essential role of CAMP factor in the cytotoxicity of P. acnes. Vaccination of mice with CAMP factor considerably reduced the growth of P. acnes and production of MIP-2, a murine counterpart of human IL-8. Acne lesions were collected from patients to establish an ex vivo acne model for validation of the efficacy of CAMP factor antibodies in the neutralization of the acne inflammatory response. The P. acnes CAMP factor and two proinflammatory cytokines (IL-8 and IL-1β) were expressed at higher levels in acne lesions than those in nonlesional skin. Incubation of ex vivo acne explants with monoclonal antibodies to CAMP factor markedly attenuated the amounts of IL-8 and IL-1β. Our work using an ex vivo acne model shows that P. acnes CAMP factor is an essential source of inflammation in acne vulgaris.

摘要

寻常痤疮影响着全球数以亿计的人群。痤疮丙酸杆菌是一种机会性皮肤细菌,与寻常痤疮的发病机制有关。我们的研究结果表明,痤疮丙酸杆菌的一种分泌性克里斯蒂-阿特金斯-芒奇-彼得森(CAMP)因子在厌氧培养中上调。CAMP 因子的突变显著降低了 P. acnes 在小鼠中的定植和炎症,表明 CAMP 因子在 P. acnes 的细胞毒性中起重要作用。用 CAMP 因子对小鼠进行疫苗接种可显著减少 P. acnes 的生长和 MIP-2 的产生,MIP-2 是人类 IL-8 的鼠类对应物。从患者收集痤疮病变以建立体外痤疮模型,以验证 CAMP 因子抗体在中和痤疮炎症反应中的功效。与非病变皮肤相比,痤疮病变中 P. acnes CAMP 因子和两种促炎细胞因子(IL-8 和 IL-1β)的表达水平更高。用 CAMP 因子的单克隆抗体孵育体外痤疮外植体可显著减少 IL-8 和 IL-1β 的含量。我们使用体外痤疮模型的工作表明,P. acnes CAMP 因子是寻常痤疮炎症的重要来源。

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