LPS stimulation

LPS 刺激
  • 文章类型: Journal Article
    甲型流感病毒(IAV)每年持续引起流行病并夺去无数人的生命。可用的治疗选择是不足的,并且用于人IAV感染的动物模型的有限相关性阻碍了新疗法的开发。生物打印的组织模型支持研究人类微组织环境中的致病机制和病原体-宿主相互作用。这里,我们描述了一个人类肺模型,它由生物打印的原代人肺成纤维细胞和单核细胞THP-1细胞组成,在其顶部打印肺泡上皮A549细胞。将细胞嵌入由藻酸盐组成的水凝胶中,明胶和胶原蛋白。这些构建体长期培养35天,它们的生存能力,分析了特定细胞标志物的表达和一般流变学参数。当模型受到细菌毒素LPS和ATP的组合攻击时,观察到促炎细胞因子IL-1β和IL-8的释放,确认该模型可以产生免疫反应。在用生物打印的肺模型进行的病毒抑制试验中,季节性IAV毒株的复制受到抗病毒药物治疗剂量依赖性的限制.打印的肺构建体提供了一个肺泡模型来研究肺病原生物学,并支持新的治疗方法的开发,不仅用于IAV,还有其他病毒。
    Influenza A virus (IAV) continuously causes epidemics and claims numerous lives every year. The available treatment options are insufficient and the limited pertinence of animal models for human IAV infections is hampering the development of new therapeutics. Bioprinted tissue models support studying pathogenic mechanisms and pathogen-host interactions in a human micro tissue environment. Here, we describe a human lung model, which consisted of a bioprinted base of primary human lung fibroblasts together with monocytic THP-1 cells, on top of which alveolar epithelial A549 cells were printed. Cells were embedded in a hydrogel consisting of alginate, gelatin and collagen. These constructs were kept in long-term culture for 35 days and their viability, expression of specific cell markers and general rheological parameters were analyzed. When the models were challenged with a combination of the bacterial toxins LPS and ATP, a release of the proinflammatory cytokines IL-1β and IL-8 was observed, confirming that the model can generate an immune response. In virus inhibition assays with the bioprinted lung model, the replication of a seasonal IAV strain was restricted by treatment with an antiviral agent in a dose-dependent manner. The printed lung construct provides an alveolar model to investigate pulmonary pathogenic biology and to support development of new therapeutics not only for IAV, but also for other viruses.
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