Paneth cell dysfunction in radiation injury and radio-mitigation by human α-defensin 5.
Paneth cell dysfunction in radiation injury and radio-mitigation by human α-defensin 5.
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放射损伤中潘氏细胞功能障碍和人α-防御素5的放射缓解作用。
DOI：
10.3389/fimmu.2023.1174140
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发表时间：
2023
影响因子：
7.3
通讯作者：
中科院分区：
文献类型：
--
作者：
辐射诱导的肠道微生物群失调的机制尚不明确。本研究检测了辐射对肠道潘氏细胞α-防御素表达的影响及其对微生物群组成和粘膜组织损伤的影响，并评价了人α-防御素5（HD 5）的放射缓解作用。成年小鼠全身照射后，通过RT-PCR检测Paneth细胞α-defensin mRNA表达，质谱检测α-defensin肽水平，评价Paneth细胞α-defensin表达。通过测量血浆脂多糖，测量FITC-菊粉的血管-管腔通量以评估肠粘膜通透性和内毒素血症。HD 5在照射前或照射后24小时在流质饮食中施用。通过16 S rRNA测序分析肠道微生物群。通过免疫荧光共聚焦显微镜分析肠上皮连接，通过细胞因子表达分析粘膜炎症反应。通过测量血浆细胞因子水平评价全身炎症。电离辐射降低了潘氏细胞α-防御素的表达，并使肠腔中的α-防御素肽耗尽。α-防御素下调与肠道菌群组成的时间依赖性改变、肠道通透性增加和内毒素血症相关。照射前24小时在饮食中给予人α-防御素5（HD 5）（预防性）可显著阻断辐射诱导的肠道微生物群失调、肠上皮紧密连接和粘附连接破坏、粘膜屏障功能障碍和粘膜炎症反应。在照射（治疗）后24小时施用的HD 5逆转了辐射诱导的微生物群生态失调、紧密连接和粘附连接破坏以及屏障功能障碍。此外，HD 5治疗还预防和逆转辐射诱导的内毒素血症和全身炎症。这些数据表明，辐射诱导肠道潘氏细胞功能障碍，HD 5喂养预防和减轻辐射诱导的肠粘膜损伤，内毒素血症和全身性炎症。
The mechanism underlying radiation-induced gut microbiota dysbiosis is undefined. This study examined the effect of radiation on the intestinal Paneth cell α-defensin expression and its impact on microbiota composition and mucosal tissue injury and evaluated the radio-mitigative effect of human α-defensin 5 (HD5). Adult mice were subjected to total body irradiation, and Paneth cell α-defensin expression was evaluated by measuring α-defensin mRNA by RT-PCR and α-defensin peptide levels by mass spectrometry. Vascular-to-luminal flux of FITC-inulin was measured to evaluate intestinal mucosal permeability and endotoxemia by measuring plasma lipopolysaccharide. HD5 was administered in a liquid diet 24 hours before or after irradiation. Gut microbiota was analyzed by 16S rRNA sequencing. Intestinal epithelial junctions were analyzed by immunofluorescence confocal microscopy and mucosal inflammatory response by cytokine expression. Systemic inflammation was evaluated by measuring plasma cytokine levels. Ionizing radiation reduced the Paneth cell α-defensin expression and depleted α-defensin peptides in the intestinal lumen. α-Defensin down-regulation was associated with the time-dependent alteration of gut microbiota composition, increased gut permeability, and endotoxemia. Administration of human α-defensin 5 (HD5) in the diet 24 hours before irradiation (prophylactic) significantly blocked radiation-induced gut microbiota dysbiosis, disruption of intestinal epithelial tight junction and adherens junction, mucosal barrier dysfunction, and mucosal inflammatory response. HD5, administered 24 hours after irradiation (treatment), reversed radiation-induced microbiota dysbiosis, tight junction and adherens junction disruption, and barrier dysfunction. Furthermore, HD5 treatment also prevents and reverses radiation-induced endotoxemia and systemic inflammation. These data demonstrate that radiation induces Paneth cell dysfunction in the intestine, and HD5 feeding prevents and mitigates radiation-induced intestinal mucosal injury, endotoxemia, and systemic inflammation.
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影响因子：
5.5
作者：
Cunliffe, RN;Mahida, YR
通讯作者：
Mahida, YR
影响因子：
2.3
作者：
Bevins, Charles L.
通讯作者：
Bevins, Charles L.
影响因子：
--
作者：
Fukui, Hiroshi
通讯作者：
Fukui, Hiroshi
DOI：
10.1152/ajpgi.1994.267.4.g709
发表时间：
1994-10-01
影响因子：
4.5
作者：
HARARI, Y;KESTER, D;CASTRO, G
通讯作者：
CASTRO, G
影响因子：
3.5
作者：
Camilleri M;Madsen K;Spiller R;Greenwood-Van Meerveld B;Verne GN
通讯作者：
Verne GN