Background

The interaction of Cryptococcus neoformans with airway epithelial cells is crucial for the establishment of cryptococcosis. Aspirin-triggered-resolvin D1 (AT-RvD1) is a lipid mediator produced during the resolution of inflammation and demonstrates anti-inflammatory and pro-resolution effects in several inflammatory experimental models including in the airways.

Method

Here, we evaluated the effects of AT-RvD1 (1, 10 or 100 nM) on human bronchial epithelial cells (BEAS-2B) stimulated with C. neoformans (1, 10 or 100 multiplicities of infection; MOI).

Results

After 24 h, C. neoformans (all MOI) demonstrated no cytotoxic effects and increased IL-8 production on BEAS-2B cells when compared to controls. In addition, C. neoformans (MOI 100) increased the concentration of IL-6, but not of IL-10. AT-RvD1 (100 nM) significantly reduced the concentration of IL-8 and IL-6 and increased IL-10 production in C. neoformans-stimulated BEAS-2B cells. C. neoformans increased the phosphorylation of NF-κB and ERK1/2, and ALX/FPR2 expression. AT-RvD1 reduced the activation of NF-kB without altering the ERK1/2 and ALX/FPR2 expression. The anti-inflammatory effects of AT-RvD1 were dependent on the ALX/FPR2, once its antagonist (BOC2) reversed its anti-inflammatory effects. No alteration on the fungal burden as well as interactions with BEAS-2B cells was observed by AT-RvD1.

Conclusion

AT-RvD1 demonstrated significant anti-inflammatory effects in bronchial epithelial cells infected with C. neoformans without affecting the development of C. neoformans infection in the airways.

Trial registration

Not applicable.

中文翻译：

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阿司匹林触发的 resolvin D1 (AT-RvD1) 在感染新型隐球菌的支气管上皮细胞中的抗炎作用

背景

新型隐球菌与气道上皮细胞的相互作用对于隐球菌病的形成至关重要。Aspirin-triggered-resolvin D1 (AT-RvD1) 是炎症消退过程中产生的一种脂质介质，在包括气道在内的多种炎症实验模型中显示出抗炎和促消退作用。

方法

在这里，我们评估了 AT-RvD1（1、10 或 100 nM）对用 C.neoformans（1、10 或 100 个感染复数；MOI）刺激的人支气管上皮细胞 (BEAS-2B) 的影响。

结果

24 小时后，与对照相比，新型隐球菌（所有 MOI）没有表现出细胞毒性作用，并且 BEAS-2B 细胞上的 IL-8 产量增加。此外，C. neoformans (MOI 100) 增加了 IL-6 的浓度，但不增加 IL-10 的浓度。AT-RvD1 (100 nM) 显着降低了新型隐球菌刺激的 BEAS-2B 细胞中 IL-8 和 IL-6 的浓度并增加了 IL-10 的产生。C. neoformans 增加了 NF-κB 和 ERK1/2 的磷酸化，以及 ALX/FPR2 的表达。AT-RvD1 在不改变 ERK1/2 和 ALX/FPR2 表达的情况下减少了 NF-kB 的激活。AT-RvD1 的抗炎作用依赖于 ALX/FPR2，一旦其拮抗剂 (BOC2) 逆转其抗炎作用。AT-RvD1 未观察到真菌负荷以及与 BEAS-2B 细胞相互作用的变化。

结论

AT-RvD1 在感染新隐球菌的支气管上皮细胞中表现出显着的抗炎作用，而不影响气道中新隐球菌感染的发展。

试用注册

不适用。