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Activation of Human Neutrophils by the Anti-Inflammatory Mediator Esenbeckia leiocarpa Leads to Atypical Apoptosis

机译:通过抗炎介质埃塞比亚雷科帕帕活化人性化粒细胞导致非典型凋亡

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Despite the fact that Esenbeckia leiocarpa, a Brazilian plant, possesses potential anti-inflammatory properties, its effect in neutrophils, key players in inflammation, has never been investigated. In this study, a crude hydroalcoholic extract (CHE) was used to evaluate the potential toxic or agonistic effect of E. leiocarpa in human neutrophils. At a noncytotoxic concentration of 500 mug/mL, CHE increased actin polymerization and cell signaling events, especially p38 MAPK. Its modulatory activity on neutrophil cell apoptosis was investigated by cytology and by flow cytometry and, although CHE increased the apoptotic rate (by cytology) and increased annexin-V binding, it did not, unexpectedly, increase CD 16 shedding. CHE increased the degradation of the cytoskeletal proteins gelsolin and paxillin but, surprisingly, not of vimentin. The proapoptotic activity of CHE was reversed by a pari-caspase inhibitor but not by a p38 inhibitor. We conclude that CHE is a novel human neutrophil agonist that induces apoptosis by a caspase-dependent and p38-independent mechanism in an atypical fashion based on its lack of effect on CD16 shedding and vimentin degradation. Since the resolution of inflammation occurs by elimination of apoptotic neutrophils, the ability of CHE to induce neutrophil apoptosis correlates well with its anti-inflammatory properties, as previously reported. Brazil boasts the greatest plant diversity on the world (approximately 55,000 species of higher plants). Brazilian plants represent a large source of potentially therapeutic compounds, a variety of which have been used in attempts to treat several infectious and/or inflammatory conditions. Esenbeckia species, such as Esenbeckia leiocarpa (Rutaceae), are wide spread in several Brazilian regions. The presence of various chemical constituents, primarily alkaloids, has already been demonstrated in this genus.
机译:尽管巴西植物埃涅贝氏雷科省具有潜在的抗炎特性,但它在炎症的关键参与者中,它在中性粒细胞中的作用从未被调查过。在该研究中,使用粗水醇提取物(Che)来评估人中中性粒细胞中E. Leiocarpa的潜在毒性或激动效果。在非酸碱浓度为500麦克风/ mL,CHE增加肌动蛋白聚合和细胞信号传导事件,尤其是P38 MAPK。通过细胞学和流式细胞术研究其对嗜中性粒细胞细胞凋亡的调节活性,但通过流式细胞术,虽然CHE增加了凋亡率(通过细胞学)并增加了annexin-v结合,但它没有意外地增加CD 16脱落。 Che增加了细胞骨骼蛋白戈尔洛林和帕西林的降解,但令人惊讶的是,不具有波形蛋白。 Che的促凋亡活性由帕利 - 胱天蛋白酶抑制剂反转,但不通过P38抑制剂逆转。我们得出结论,Che是一种新型人中性粒细胞激动剂,其基于缺乏对CD16脱落和平衡降解的影响,以非典型方式诱导凋亡和P38独立机制的细胞凋亡。由于通过消除凋亡的中性粒细胞来发生炎症的分辨率,因此如前所述,Che诱导中性粒细胞凋亡的能力与其抗炎性质相关。巴西在世界上拥有最大的植物多样性(大约55,000种高等植物)。巴西植物代表潜在治疗化合物的大来源,各种潜在的潜在治疗化合物,用于治疗几种感染性和/或炎症病症的尝试。 Esenbeckia物种,例如Esenbeckia Leiocarpa(芸香貂),在几个巴西地区广泛传播。在该属中已经证明了各种化学成分,主要是生物碱的存在。

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