Department of Chemistry and Biochemistry, School of Medicine, University of Rijeka, Rijeka, Croatia.
J Cell Biochem. 2011 Nov;112(11):3322-33. doi: 10.1002/jcb.23261.
Causal connections between dipeptidyl peptidase IV, also known as CD26 molecule (DPP IV/CD26) and inflammatory bowel disease (IBD) have been shown, but mechanisms of these interactions are unclear. Our hypothesis was that DPP IV/CD26 could affect the neuroimmune response during inflammatory events. Therefore, we aimed to evaluate its possible role and the relevance of the gut-brain axis in a model of IBD in mice. Trinitrobenzenesulfonic acid-induced (TNBS) colitis was induced in CD26-deficient (CD26(-/-) ) and wild-type (C57BL/6) mice. Pathohistological and histomorphometrical measurements were done. Concentrations and protein expressions of DPP IV/CD26 substrates neuropeptide Y (NPY) and vasoactive intestinal peptide (VIP) were determined. Concentrations of IL-6 and IL-10 were evaluated. Investigations were conducted at systemic and local levels. Acute inflammation induced increased serum NPY concentrations in both mice strains, more enhanced in CD26(-/-) mice. Increased NPY concentrations were found in colon and brain of C57BL/6 mice, while in CD26(-/-) animals only in colon. VIP and IL-6 serum and tissue concentrations were increased in both mice strains in acute inflammation, more pronouncedly in CD26(-/-) mice. IL-10 concentrations, after a decrease in serum of both mice strains, increased promptly in CD26(-/-) mice. Decreased IL-10 concentration was found in brain of C57BL/6 mice, while it was increased in colon of CD26(-/-) mice in acute inflammation. DPP IV/CD26 deficiency affects the neuroimmune response at systemic and local levels during colitis development and resolution in mice. Inflammatory changes in the colon reflected on investigated parameters in the brain, suggesting an important role of the gut-brain axis in IBD pathogenesis.
二肽基肽酶 IV（也称为 CD26 分子，DPP IV/CD26）与炎症性肠病（IBD）之间的因果关系已被证实，但这些相互作用的机制尚不清楚。我们的假设是 DPP IV/CD26 可能会影响炎症事件期间的神经免疫反应。因此，我们旨在评估其在小鼠 IBD 模型中的可能作用及其与肠-脑轴的相关性。在 CD26 缺陷型（CD26(-/-)）和野生型（C57BL/6）小鼠中诱导三硝基苯磺酸（TNBS）结肠炎。进行组织病理学和组织形态计量学测量。测定 DPP IV/CD26 底物神经肽 Y（NPY）和血管活性肠肽（VIP）的浓度和蛋白表达。评估 IL-6 和 IL-10 的浓度。在全身和局部水平进行研究。急性炎症在两种小鼠品系中均导致血清 NPY 浓度升高，在 CD26(-/-) 小鼠中更为明显。C57BL/6 小鼠的结肠和脑中均发现 NPY 浓度增加，而在 CD26(-/-) 动物中仅在结肠中发现。在急性炎症中，两种小鼠品系的 VIP 和 IL-6 血清和组织浓度均升高，在 CD26(-/-) 小鼠中更为明显。两种小鼠品系的血清 IL-10 浓度均先降低后迅速增加在 CD26(-/-) 小鼠中。C57BL/6 小鼠的脑中发现 IL-10 浓度降低，而在 CD26(-/-) 小鼠的结肠中增加。在结肠炎的发展和缓解过程中，DPP IV/CD26 缺乏会影响全身和局部水平的神经免疫反应。结肠中的炎症变化反映在大脑中研究的参数上，表明肠-脑轴在 IBD 发病机制中具有重要作用。
