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Human-derived cathelicidin LL-37 directly activates mast cells to proinflammatory mediator synthesis and migratory response

机译:人类来源的cathelicidin LL-37直接激活肥大细胞以促炎介质合成和迁移反应

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摘要

Cathelicidins, a family of antimicrobial peptides, are well known for their role in host defense, particularly against bacteria. Apart from direct killing of microbes through the membrane disruption, cathelicidins can also exert immunomodulatory effects on cells involved in inflammatory processes. Considering the important role of mast cells in inflammation, the aim of this study was to determine whether LL-37, human-derived cathelicidin, can induce mast cell activation. We have observed that LL-37 directly stimulates mast cell to degranulation and production of some proinflammatory cytokines, but fails to induce cysteinyl leukotriene generation and release. We have also documented that LL-37 acts as a strong mast cell chemoattractant. In intracellular signaling in mast cells activated by LL-37 participates PLC/A(2) and, in part, MAPKs, and PI3K. In conclusion, our results indicate that cathelicidins may enhance antibacterial inflammatory response via attracting mast cell to pathogen entry site and via induction of mast cell-derived mediator release. (C) 2014 Elsevier Inc. All rights reserved.
机译:鞘磷脂,一种抗菌肽家族,因其在宿主防御中的作用,尤其是针对细菌的防御作用而闻名。除了通过膜破坏直接杀死微生物外,Cathelicidins还可以对参与炎症过程的细胞产生免疫调节作用。考虑到肥大细胞在炎症中的重要作用,本研究的目的是确定人源的cathelicidin LL-37是否可以诱导肥大细胞活化。我们已经观察到,LL-37直接刺激肥大细胞脱粒并产生某些促炎细胞因子,但不能诱导半胱氨酰白三烯的产生和释放。我们还记录了LL-37可以作为一种强大的肥大细胞化学引诱剂。在由LL-37激活的肥大细胞的细胞内信号传导中,参与PLC / A(2),部分参与MAPK和PI3K。总之,我们的结果表明,cathelicidins可能通过将肥大细胞吸引到病原体进入部位和诱导肥大细胞衍生的介质释放来增强抗菌炎症反应。 (C)2014 Elsevier Inc.保留所有权利。

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