Data from: Recombinant human IL-26 facilitates the innate immune response to endotoxin in the bronchoalveolar space of mice in vivo

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Interleukin (IL)-26 is released in response to bacterial endotoxin (LPS) in the bronchoalveolar space of humans in vivo and it may potentiate neutrophil chemotaxis by enhanced IL-26 receptor stimulation. However, the effects of extracellular IL-26 protein on the innate immune response in the lungs in vivo remain unknown. Here, we characterized these effects of IL-26 on a wide range of aspects of the innate immune response to LPS in different compartments of the lungs in vivo over time. We administrated recombinant human (rh) IL-26 protein in the bronchoalveolar space using intranasal instillation in a mouse in vivo model, with and without prior instillation of LPS. We verified gene expression of the IL-26 receptor complex in mouse lungs and observed that, after instillation of LPS, rhIL-26 increases the phosphorylation of STAT3, a signaling molecule of the IL-26 receptor complex. We also observed that rhIL-26 exerted additional stimulatory and inhibitory actions that are compartment- and time-dependent, resulting in alterations of cytokines, proteinases, tissue inflammation and the accumulation of innate effector cells. Without the prior instillation of LPS, rhIL-26 exerted time-dependent effects on total gelatinase activity but few other effects. Most important, after instillation of LPS, rhIL-26 cleared inflammatory cells from local tissue and increased the accumulation of innate effector cells in the bronchoalveolar space. Tentatively, rhIL-26 may facilitate the innate immune response towards the bronchoalveolar space in vivo and represents a potential target for therapy in lung disorders involving the innate immune response.

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白细胞介素(Interleukin, IL)-26可在人体体内支气管肺泡腔中响应细菌内毒素(LPS)释放，并通过增强IL-26受体的刺激作用促进中性粒细胞趋化。然而目前学界尚未明确细胞外IL-26蛋白对体内肺部先天免疫应答的具体影响。本研究针对体内不同肺腔室中，IL-26随时间变化对LPS诱导的先天免疫应答的多方面影响进行了系统表征。

我们通过鼻内滴注法，在小鼠体内模型的支气管肺泡腔中给予重组人(recombinant human, rh)IL-26蛋白，并设置预先滴注LPS与未预先滴注LPS两组对照。我们验证了小鼠肺部IL-26受体复合物的基因表达情况，且观察到在滴注LPS后，rhIL-26可增强IL-26受体复合物的信号分子信号转导与转录激活因子3(STAT3)的磷酸化水平。同时研究发现，rhIL-26可发挥具有腔室特异性与时间依赖性的额外刺激与抑制作用，进而改变细胞因子、蛋白水解酶、组织炎症状态以及先天效应细胞的聚集模式。

在未预先滴注LPS的情况下，rhIL-26仅对明胶酶总活性产生时间依赖性影响，其余效应并不显著。最为关键的是，在滴注LPS后，rhIL-26可清除局部组织中的炎症细胞，并促进先天效应细胞在支气管肺泡腔中的聚集。初步推测，rhIL-26可在体内促进针对支气管肺泡腔的先天免疫应答，有望成为涉及先天免疫应答的肺部疾病的潜在治疗靶点。