Alcohol Research Program, Burn and Shock Trauma Research Institute, Department of Surgery, Loyola University Chicago Health Sciences Campus, Maywood, Illinois, USA.
Integrative Cell Biology Program, Loyola University Chicago Health Sciences Campus, Maywood, Illinois, USA.
J Leukoc Biol. 2022 Dec;112(6):1471-1484. doi: 10.1002/JLB.4A0122-068R. Epub 2022 Aug 2.
Ulcerative colitis (UC) is characterized by cycles of active disease flare and inactive disease remission. During UC remission, IL-22 is up-regulated, acting as a hallmark of entrance into UC remission. Recently, we found that in our mouse model of binge alcohol and dextran sodium sulfate (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 with DSS vehicle. Examination of lamina propria (LP) cells in the large intestine revealed IL-22+ γδ 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 L. delbrueckii supernatant was not sufficient to reduce UC exacerbation following alcohol. Our findings suggest L. 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.
溃疡性结肠炎（UC）的特征是疾病活动期发作和非活动期缓解的周期。在 UC 缓解期，IL-22 上调，作为进入 UC 缓解的标志。最近，我们在酒精和葡聚糖硫酸钠（DSS）诱导的结肠炎的小鼠模型中发现，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 持续存在，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 载体相比，DSS 乙醇中大肠 IL-22 的水平显著降低了约 6.9 倍。在 DSS 载体处理的小鼠中，观察到大肠固有层（LP）细胞中的 IL-22+γδ T 细胞显著增加，而 DSS 乙醇小鼠中的 IL-22+γδ T 细胞无法产生这种 IL-22 反应。我们给予 rIL-22，发现它恢复了 DSS 乙醇处理小鼠的体重减轻。结肠缩短和肠杆菌科增加也得到缓解。给予德氏乳杆菌 attenuatus 减轻了体重减轻（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，并使 DSS 乙醇小鼠的 p-STAT3 水平恢复到 DSS 载体组的水平。相比之下，单独给予德氏乳杆菌 attenuatus 上清液不足以减少酒精后 UC 的恶化。我们的研究结果表明，德氏乳杆菌 attenuatus 通过增加 IL-22 的水平来促进修复机制，从而导致 STAT3 的磷酸化，从而减轻结肠炎后酒精引起的肠道损伤的增加。
