Interleukin-22 Prevents Microbial Dysbiosis and Promotes Intestinal Barrier Regeneration Following Acute Injury.
Interleukin-22 Prevents Microbial Dysbiosis and Promotes Intestinal Barrier Regeneration Following Acute Injury.
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DOI：
10.1097/shk.0000000000000900
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发表时间：
2017-12
期刊：
影响因子：
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通讯作者：
Choudhry MA
中科院分区：
文献类型：
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作者：
Hammer AM;Morris NL;Cannon AR;Khan OM;Gagnon RC;Movtchan NV;van Langeveld I;Li X;Gao B;Choudhry MA
肠屏障破坏和细菌移位可导致脓毒症和多器官功能衰竭，这是烧伤患者死亡的主要原因。此外，研究结果表明，乙醇（酒精）中毒时，受伤的症状与烧伤。我们以前已经表明，白细胞介素-22（IL-22）保护肠渗漏，并防止乙醇和烧伤后革兰氏阴性菌的过度生长，但IL-22如何介导这些作用尚未确定。在这里，利用模型的乙醇和烧伤，我们表明，联合侮辱的结果在小肠隐窝内的增殖细胞的显着损失，并增加肠杆菌科的副本，尽管水平升高的抗微生物肽（AMP）脂质运载蛋白-2。IL-22给药恢复了隐窝内增殖细胞的数量，显著增加了肠上皮细胞中Reg 3 β、Reg 3 γ、脂质运载蛋白-2 AMP转录物水平，并导致小肠中肠杆菌科细菌的完全减少。敲除肠上皮细胞中的信号转导子和转录激活因子-3（STAT 3）导致IL-22保护的完全丧失，表明STAT 3是乙醇联合损伤后肠屏障保护所需的。总之，这些发现表明IL-22/STAT 3信号传导对肠道屏障完整性至关重要，并且针对该途径可能在烧伤后具有有益的临床意义。
Intestine barrier disruption and bacterial translocation can contribute to sepsis and multiple organ failure- leading causes of mortality in burn-injured patients. Additionally, findings suggest ethanol (alcohol) intoxication at the time of injury worsens symptoms associated with burn injury. We have previously shown that interleukin-22 (IL-22) protects from intestinal leakiness and prevents overgrowth of Gram-negative bacteria following ethanol and burn injury, but how IL-22 mediates these effects has not been established. Here, utilizing a model of ethanol and burn injury, we show that the combined insult results in a significant loss of proliferating cells within small intestine crypts and increases Enterobacteriaceae copies, despite elevated levels of the anti-microbial peptide (AMPs) lipocalin-2. IL-22 administration restored numbers of proliferating cells within crypts, significantly increased Reg3β, Reg3γ, lipocalin-2 AMP transcript levels in intestine epithelial cells, and resulted in complete reduction of Enterobacteriaceae in the small intestine. Knockout of signal transducer and activator of transcription factor-3 (STAT3) in intestine epithelial cells resulted in complete loss of IL-22 protection, demonstrating STAT3 is required for intestine barrier protection following ethanol combined with injury. Together, these findings suggest IL-22/STAT3 signaling is critical to gut barrier integrity and targeting this pathway may be of beneficial clinical relevance following burn injury.