Lipopolysaccharide-Induced Inflammatory Cytokine Expression in Taste Organoids
Lipopolysaccharide-Induced Inflammatory Cytokine Expression in Taste Organoids
复制标题
味觉类器官中脂多糖诱导的炎症细胞因子表达
DOI：
10.1093/chemse/bjaa002
复制
发表时间：
2020-03-01
期刊：
影响因子：
3.5
通讯作者：
Wang, Hong
中科院分区：
文献类型：
--
作者：
Feng, Shan;Achoute, Leyitha;Wang, Hong
炎性细胞因子是调节从组织稳态到代谢和食物摄入的许多生理过程的信号分子。急性和慢性炎症可诱导味蕾细胞亚群表达某些细胞因子。这可能导致与许多疾病相关的味觉和偏好改变。虽然细胞因子诱导的途径在免疫细胞中得到了很好的研究，但它们在味觉细胞中的特征仍然很差，部分原因是难以用有限数量的味觉细胞进行生化分析。最近开发的味觉类器官模型提供了一个机会，在体外进行这些机制的研究。然而，尚不清楚味觉类器官是否像体内天然味蕾一样对炎症刺激做出反应。在这里，我们分析脂多糖（LPS）诱导的表达和分泌的两种炎症细胞因子，肿瘤坏死因子（TNF）和白细胞介素-6（IL-6）。我们发现，与天然小鼠味觉上皮细胞类似，来自小鼠轮廓干细胞的类器官表达几种Toll样受体（TLR），包括LPS的主要受体TLR 4。类器官和天然味觉上皮表达核因子-κ B（Nfkb）家族中编码转录因子NF-κ B（炎症反应的关键调节因子）的所有五种基因。LPS刺激TNF和IL-6的快速诱导，在类器官和天然味觉上皮中具有相似的诱导动力学。这些结果表明，味觉上皮细胞具有炎症细胞因子的诱导和分泌的必要组件，并建议类器官模型可以是一个有用的工具来剖析潜在的机制。
Inflammatory cytokines are signaling molecules that regulate numerous physiological processes, from tissue homeostasis to metabolism and food intake. Expression of certain cytokines can be markedly induced in subsets of taste bud cells under acute and chronic inflammation. This may contribute to altered taste perception and preference associated with many diseases. Although the pathways of cytokine induction are well studied in immune cells, they remain poorly characterized in taste cells, in part due to the difficulties of performing biochemical analyses with a limited number of taste cells. The recently developed taste organoid model provides an opportunity to carry out these mechanistic studies in vitro. However, it was unknown whether taste organoids respond to inflammatory stimuli as do in vivo native taste buds. Here we analyze lipopolysaccharide (LPS)-induced expression and secretion of two inflammatory cytokines, tumor necrosis factor (TNF), and interleukin-6 (IL-6). We show that, similarly to native mouse taste epithelia, organoids derived from mouse circumvallate stem cells express several toll-like receptors (TLRs), including TLR4-the primary receptor for LPS. Organoids and native taste epithelia express all five genes in the nuclear factor-kappa b (Nfkb) family that encode the transcription factor NF-kappa B, a critical regulator of inflammatory responses. LPS stimulates fast induction of TNF and IL-6 with similar induction kinetics in organoids and native taste epithelia. These results show that taste epithelial cells possess necessary components for inflammatory cytokine induction and secretion and suggest that the organoid model can be a useful tool to dissect the underlying mechanisms.