Department of Biochemistry and Molecular Biology II, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), School of Pharmacy, Instituto de Investigación Biosanitario (IBIG), University of Granada, Campus de Cartuja s/n, 18071 Granada, Spain.
Department of Pharmacology, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), School of Pharmacy, Instituto de Investigación Biosanitario (IBIG), University of Granada, Campus de Cartuja s/n, 18071 Granada, Spain.
Br J Nutr. 2014 Apr 14;111(7):1202-12. doi: 10.1017/S0007114513003590. Epub 2013 Nov 14.
Milk κ-casein-derived bovine glycomacropeptide (GMP) exerts immunomodulatory effects. It exhibits intestinal anti-inflammatory activity in chemically induced models of colitis. However, to validate its clinical usefulness as a nutraceutical, it is important to assess its effects in a model with a closer pathophysiological connection with human inflammatory bowel disease. Therefore, in the present study, we used the lymphocyte-transfer model of colitis in mice and compared the effects of GMP in this model with those obtained in the dextran sulphate sodium (DSS) model. GMP (15 mg/d) resulted in higher body-weight gain and a reduction of the colonic damage score and myeloperoxidase (MPO) activity in Rag1(-/-) mice with colitis induced by the transfer of naïve T cells. The colonic and ileal weight:length ratio was decreased by approximately 25%, albeit non-significantly. GMP treatment reduced the percentage of CD4⁺ interferon (IFN)-γ⁺ cells in mesenteric lymph nodes (MLN). The basal production of IL-6 by MLN obtained from the GMP-treated mice ex vivo was augmented. However, concanavalin A-evoked production was similar. The colonic expression of regenerating islet-derived protein 3γ, S100A8, chemokine (C-X-C motif) ligand 1 and IL-1β was unaffected by GMP, while that of TNF-α and especially IFN-γ was paradoxically increased. In the DSS model, GMP also reduced the activity of colonic MPO, but it failed to alter weight gain or intestinal weight:length ratio. GMP augmented the production of IL-10 by MLN cells and was neutral towards other cytokines, except exhibiting a trend towards increasing the production of IL-6. The lower effect was attributed to the lack of the effect of GMP on epithelial cells. In conclusion, GMP exerts intestinal anti-inflammatory effects in lymphocyte-driven colitis.
牛奶κ-酪蛋白衍生的牛糖巨肽（GMP）具有免疫调节作用。它在化学诱导的结肠炎模型中表现出肠道抗炎活性。然而，为了验证其作为营养保健品的临床实用性，重要的是要在与人类炎症性肠病更接近的病理生理学联系的模型中评估其效果。因此，在本研究中，我们使用了小鼠淋巴细胞转移结肠炎模型，并比较了 GMP 在该模型中的作用与在葡聚糖硫酸钠（DSS）模型中获得的作用。在由幼稚 T 细胞转移引起的 Rag1（-/-）结肠炎小鼠中，GMP（15mg/d）导致体重增加更多，结肠损伤评分和髓过氧化物酶（MPO）活性降低。尽管非显着，但结肠和回肠重量-长度比降低了约 25%。GMP 治疗可降低肠系膜淋巴结（MLN）中 CD4+干扰素（IFN）-γ+细胞的百分比。从接受 GMP 治疗的小鼠中获得的 MLN 的基础 IL-6 产生增加。然而，刀豆球蛋白 A 诱发的产生是相似的。GMP 对再生胰岛衍生蛋白 3γ、S100A8、趋化因子（C-X-C 基序）配体 1 和 IL-1β 的结肠表达没有影响，而 TNF-α和特别是 IFN-γ的表达则被悖论性地增加。在 DSS 模型中，GMP 还降低了结肠 MPO 的活性，但未能改变体重增加或肠道重量-长度比。GMP 增强了 MLN 细胞产生的 IL-10，并对其他细胞因子呈中性，除了表现出增加 IL-6 产生的趋势。较低的作用归因于 GMP 对上皮细胞缺乏作用。总之，GMP 在淋巴细胞驱动的结肠炎中发挥肠道抗炎作用。
