A multi-mineral intervention to counter pro-inflammatory activity and to improve the barrier in human colon organoids.
A multi-mineral intervention to counter pro-inflammatory activity and to improve the barrier in human colon organoids.
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DOI：
10.3389/fcell.2023.1132905
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发表时间：
2023
影响因子：
5.5
通讯作者：
中科院分区：
文献类型：
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作者：
前言：溃疡性结肠炎是一种慢性炎症性疾病，持续的炎症刺激可能导致屏障功能障碍。本研究的目的是通过红藻衍生的多矿物质干预在促炎性损伤存在或不存在的情况下评估屏障蛋白质组的表达。 研究方法：将人结肠类器官单独维持在对照培养基中或暴露于脂多糖与三种促炎细胞因子[肿瘤坏死因子-α、白细胞介素-1 β和干扰素-γ（LPS-细胞因子）]的组合以模拟发炎结肠中的环境。将未处理的类器官和暴露于LPS-细胞因子的类器官用先前已显示改善屏障结构/功能的多矿物质产品（Aquamin®）伴随处理14天。对结肠类器官进行蛋白质组学分析，以获得由两种干预单独和组合诱导的蛋白质变化的广泛观点。同时，共聚焦荧光显微镜，组织凝聚力和跨上皮电阻（TEER）测量用于评估屏障结构/功能。 结果：LPS-细胞因子混合物改变了影响先天免疫和促进炎症的多种蛋白质的表达。单独使用Aquamin®时，这些蛋白质中的几种显著降低，但在LPS-细胞因子存在下，通过Aquamin®检测到这些蛋白质的一个亚组仅适度降低。其中，包括纤维蛋白原-β和-γ链（FGB和FGG）、磷脂酶A2（PLA 2G 2A）和β-内酰胺酶的炎症相关蛋白质的子集在Aquamin®（单独和与LPS-细胞因子组合）存在下显著下调;具有抗炎、抗氧化或抗微生物活性的蛋白质的另一个子集通过Aquamin®处理上调。当单独提供时，Aquamin®强烈上调有助于屏障形成和组织强度的蛋白质。与LPS-细胞因子的伴随治疗不抑制响应Aquamin®的屏障形成。共聚焦显微镜还显示单独或在促炎刺激物存在下，用Aquamin®增加桥粒芯糖蛋白-2（DSG 2）和钙粘蛋白-17（CDH 17）的表达。用Aquamin®（单独或在LPS-细胞因子存在下）增加的凝聚力和TEER表明屏障功能改善。 结论：总之，这些发现表明，多矿物质干预（Aquamin®）可以通过改善屏障结构/功能以及直接改变某些促炎蛋白的表达来提供一种对抗结肠炎症的新方法。
Introduction: Ulcerative colitis is a chronic inflammatory condition, and continuous inflammatory stimulus may lead to barrier dysfunction. The goal of this study was to assess barrier proteomic expression by a red algae-derived multi-mineral intervention in the absence or presence of pro-inflammatory insult. Methods: Human colon organoids were maintained in a control culture medium alone or exposed to lipopolysaccharide with a combination of three pro-inflammatory cytokines [tumor necrosis factor-α, interleukin-1β and interferon-γ (LPS-cytokines)] to mimic the environment in the inflamed colon. Untreated organoids and those exposed to LPS-cytokines were concomitantly treated for 14 days with a multi-mineral product (Aquamin®) that has previously been shown to improve barrier structure/function. The colon organoids were subjected to proteomic analysis to obtain a broad view of the protein changes induced by the two interventions alone and in combination. In parallel, confocal fluorescence microscopy, tissue cohesion and transepithelial electrical resistance (TEER) measurements were used to assess barrier structure/function. Results: The LPS-cytokine mix altered the expression of multiple proteins that influence innate immunity and promote inflammation. Several of these were significantly decreased with Aquamin® alone but only a modest decrease in a subset of these proteins was detected by Aquamin® in the presence of LPS-cytokines. Among these, a subset of inflammation-related proteins including fibrinogen-β and -γ chains (FGB and FGG), phospholipase A2 (PLA2G2A) and SPARC was significantly downregulated in the presence of Aquamin® (alone and in combination with LPS-cytokines); another subset of proteins with anti-inflammatory, antioxidant or anti-microbial activity was upregulated by Aquamin® treatment. When provided alone, Aquamin® strongly upregulated proteins that contribute to barrier formation and tissue strength. Concomitant treatment with LPS-cytokines did not inhibit barrier formation in response to Aquamin®. Confocal microscopy also displayed increased expression of desmoglein-2 (DSG2) and cadherin-17 (CDH17) with Aquamin®, either alone or in the presence of the pro-inflammatory stimulus. Increased cohesion and TEER with Aquamin® (alone or in the presence of LPS-cytokines) indicates improved barrier function. Conclusion: Taken together, these findings suggest that multi-mineral intervention (Aquamin®) may provide a novel approach to combating inflammation in the colon by improving barrier structure/function as well as by directly altering the expression of certain pro-inflammatory proteins.
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影响因子：
7.3
作者：
Chang, Ya-Yun;Yu, Linda Chia-Hui;Jeng, Yung-Ming
通讯作者：
Jeng, Yung-Ming
影响因子：
7.2
作者：
Aviello, Gabriella;Amu, Sylvie;Fallon, Padraic G.
通讯作者：
Fallon, Padraic G.
影响因子：
4
作者：
Cirillo, Nicola;Lanza, Michele;Lanza, Alessandro
通讯作者：
Lanza, Alessandro
影响因子：
3.9
作者：
Tyszka M;Biliński J;Basak GW
通讯作者：
Basak GW
影响因子：
3.9
作者：
Coskun M
通讯作者：
Coskun M