Bioscience Research Institute, Athlone Institute of Technology, Athlone, Ireland; Department of Graduate Studies, Limerick Institute of Technology, Limerick, Ireland.
Lung Biology Group, Regenerative Medicine Institute at CURAM Centre for Medical Devices, School of Medicine, National University of Ireland Galway, Galway, Ireland; Anaesthesia and Intensive Care Medicine, University Hospital Galway, Galway, Ireland; Department of Medicine and Surgery, University of Milan-Bicocca, Monza, Italy.
Sci Total Environ. 2022 Feb 25;809:152177. doi: 10.1016/j.scitotenv.2021.152177. Epub 2021 Dec 4.
Acute respiratory distress syndrome (ARDS) is the most common form of acute severe hypoxemic respiratory failure in the critically ill with a hospital mortality of 40%. Alveolar inflammation is one of the hallmarks for this disease. β-Glucans are polysaccharides isolated from a variety of natural sources including mushrooms, with documented immune modulating properties. To investigate the immunomodulatory activity of β-glucans and their potential as a treatment for ARDS, we isolated and measured glucan-rich polysaccharides from seven species of mushrooms. We used three models of in-vitro injury in THP-1 macrophages, Peripheral blood mononuclear cells (CD14+) (PMBCs) isolated from healthy volunteers and lung epithelial cell lines. We observed variance between β-glucan content in extracts isolated from seven mushroom species. The extracts with the highest β-glucan content found was Lentinus edodes which contained 70% w/w and Hypsizygus tessellatus which contained 80% w/w with low levels of α-glucan. The extracts had the ability to induce secretion of up to 4000 pg/mL of the inflammatory cytokine IL-6, and up to 5000 pg/mL and 500 pg/mL of the anti-inflammatory cytokines IL-22 and IL-10, respectively, at a concentration of 1 mg/mL in THP-1 macrophages. In the presence of cytokine injury, IL-8 was reduced from 15,000 pg/mL to as low as 10,000 pg/mL in THP-1 macrophages. After insult with LPS, phagocytosis dropped from 70-90% to as low 10% in CD14+ PBMCs. After LPS insult CCL8 relative gene expression was reduced, and IL-10 relative gene expression increased from 50 to 250-fold in THP-1 macrophages. In lung epithelial cells, both A549 and BEAS-2B after IL-1β insult, IL-8 levels dropped from 10,000 pg/mL to as low as 6000 pg/mL. TNF-α levels dropped 10-fold from 100 pg/mL to just below 10 pg/mL. These results demonstrate the therapeutic potential of β-glucans in inflammatory lung conditions. Findings also advance bio-based research that connects green innovation with One Health applications for the betterment of society.
急性呼吸窘迫综合征（ARDS）是危重病患者中最常见的急性严重低氧性呼吸衰竭形式，其住院死亡率为 40%。肺泡炎症是该疾病的标志之一。β-葡聚糖是从各种天然来源（包括蘑菇）中分离出的多糖，具有已证实的免疫调节特性。为了研究β-葡聚糖的免疫调节活性及其作为 ARDS 治疗方法的潜力，我们从七种蘑菇中分离并测量了富含葡聚糖的多糖。我们使用三种体外损伤模型，即 THP-1 巨噬细胞、来自健康志愿者的外周血单核细胞（CD14+）（PMBC）和肺上皮细胞系。我们观察到从七种蘑菇物种中分离出的提取物中的β-葡聚糖含量存在差异。提取物中β-葡聚糖含量最高的是香菇，含量为 70%w/w，其次是绣球菌，含量为 80%w/w，α-葡聚糖含量较低。提取物在 THP-1 巨噬细胞中浓度为 1mg/mL 时，具有诱导高达 4000pg/mL 炎性细胞因子 IL-6、高达 5000pg/mL 和 500pg/mL 抗炎细胞因子 IL-22 和 IL-10 的分泌的能力。在细胞因子损伤存在的情况下，IL-8 从 THP-1 巨噬细胞中的 15000pg/mL 降低至低至 10000pg/mL。在 LPS 损伤后，CD14+PBMC 中的吞噬作用从 70-90%降低至低至 10%。在 LPS 损伤后，CCL8 的相对基因表达减少，而 THP-1 巨噬细胞中的 IL-10 相对基因表达增加了 50 至 250 倍。在肺上皮细胞中，IL-1β 损伤后 A549 和 BEAS-2B，IL-8 水平从 10000pg/mL 降低至低至 6000pg/mL。TNF-α 水平从 100pg/mL 降低 10 倍至略低于 10pg/mL。这些结果表明β-葡聚糖在炎症性肺部疾病中的治疗潜力。这些发现还推进了将绿色创新与“同一健康”应用联系起来的基于生物的研究，以造福社会。
