IL-22 and Lactobacillus delbrueckii mitigate alcohol-induced exacerbation of DSS-induced colitis.
IL-22 and Lactobacillus delbrueckii mitigate alcohol-induced exacerbation of DSS-induced colitis.
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IL-22 和德氏乳杆菌可减轻酒精引起的 DSS 诱导的结肠炎恶化。
DOI：
10.1002/jlb.4a0122-068r
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发表时间：
2022-12
影响因子：
5.5
通讯作者：
Choudhry, Mashkoor A.
中科院分区：
文献类型：
--
作者：
Cannon, Abigail R.;Shim, Esther H.;Kuprys, Paulius, V;Choudhry, Mashkoor A.
溃疡性结肠炎（UC）的特征是活动性疾病发作和非活动性疾病缓解的周期。在UC缓解期间，IL-22上调，作为进入UC缓解的标志。最近，我们发现在我们的酗酒和DSS诱导的结肠炎小鼠模型中，酒精增加了UC病理的严重程度。在这项研究中，我们不仅评估了酒精是否影响IL-22的表达，从而使UC永久化，而且还评估了重组IL-22（rIL-22）或益生菌治疗是否可以缓解UC的恶化症状。与DSS溶剂相比，DSS乙醇中大肠IL-22的水平显著降低约6.9倍。大肠中固有层（LP）细胞的检查显示，DSS媒介物处理的小鼠中的IL-22+ γ δ T细胞显著增加，而DSS乙醇小鼠中的IL-22+ γδ T细胞不能产生这种IL-22应答。我们给予rIL-22，发现它恢复了DSS乙醇治疗小鼠的体重减轻。结肠缩短和肠杆菌增加也减弱。在DSS乙醇小鼠中，德氏乳杆菌的施用减弱了体重减轻（p<0.01）、结肠长度（p<0.001）、减轻了肠杆菌科的增加、增加了IL-22的水平和增加了p-STAT 3的水平，回到DSS媒介物组的水平。相反，单独施用德氏乳杆菌上清液不足以减少酒精后的UC恶化。我们的研究结果表明，德氏乳杆菌通过增加IL-22的水平，导致STAT 3的磷酸化，从而减轻结肠炎后酒精诱导的肠道损伤增加，从而有助于修复机制。
Ulcerative colitis (UC) is characterized by cycles of active disease flare and inactive disease remission. During UC remission, IL-22 is upregulated, acting as a hallmark of entrance into UC remission. Recently, we found that in our mouse model of binge alcohol and DSS-induced colitis, alcohol increases severity of UC pathology. In this study, we assessed not only whether alcohol influenced IL-22 expression and thereby perpetuates UC, but also whether recombinant IL-22 (rIL-22) or treatment with a probiotic could alleviate exacerbated symptoms of UC. Levels of large intestine IL-22 were significantly decreased ~6.9 fold in DSS Ethanol compared to DSS Vehicle. Examination of lamina propria (LP) cells in the large intestine revealed IL-22+ γ T cells in DSS Vehicle treated mice were significantly increased, while IL-22+ γδ T cells in DSS Ethanol mice were unable to mount this IL-22 response. We administered rIL-22 and found it restored weight loss of DSS Ethanol treated mice. Colonic shortening and increased Enterobacteriaceae were also attenuated. Administration of Lactobacillus delbrueckii attenuated weight loss (p<0.01), colon length (p<0.001), mitigated increases in Enterobacteriaceae, increased levels of IL-22, and increased levels of p-STAT3 back to that of DSS Vehicle group in DSS Ethanol mice. In contrast, sole administration of Lactobacillus delbrueckii supernatant was not sufficient to reduce UC exacerbation following alcohol. Our findings suggest Lactobacillus delbrueckii contributes to repair mechanisms by increasing levels of IL-22, resulting in phosphorylation of STAT3, thus attenuating the alcohol induced increases in intestinal damage after colitis.