Bleau C, Lamontagne L, Savard R
Département des Sciences Biologiques, Université du Québec à Montréal, Montréal, Québec, Canada.
Clin Exp Immunol. 2005 Jun;140(3):427-35. doi: 10.1111/j.1365-2249.2005.02785.x.
Leptin produced by adipocytes increases Th1-dependent immunostimulation and autoimmune diseases. Lactobacilli are known to promote or suppress Th1 responses according to the isolates. We have investigated whether the sensitivity of Suriss Jim Lambert (SJL) mice to Th1-dependent immune diseases, when compared with C57BL/6 mice, may be modulated by selected lactobacilli able to decrease leptin release by adipocytes. White adipocytes were isolated from both C57BL/6 and SJL mice and incubated with bacterial extracts from new CBA4P and TPA3P isolates of Lactobacillus acidophilus and L. rhamnosus 9595 (LR), or with conditioned media (CM) from lactobacillus-treated macrophages. Immunomodulation induced by supernatants of treated adipocytes was determined by metabolic activity of syngenic splenic lymphocytes. Leptin produced by adipocytes, tumour necrosis factor (TNF)-alpha and interleukin (IL)-1beta by macrophages, and IFN-gamma and IL-4 by lymphocytes were quantified by enzyme-linked immunosorbent assay (ELISA) tests. Results revealed that supernatants from CBA4P- and LR-treated adipocytes decreased the metabolic activity of lymphocytes from SJL mice, whereas adipocytes incubated with CM from CBA4P-treated macrophages showed no stimulation of lymphocytes. Such effects correlated with leptin levels. Lower levels of leptin were produced by adipocytes from SJL mice in the presence of CBA4P and LR extracts. Lymphocytes from SJL mice produced low levels of IFN-gamma when incubated with supernatants from CBA4P-treated cells. Such immunosuppressive effects were dependent on levels of TNF-alpha and IL-1beta produced by lactobacillus-treated macrophages. Taken together, these results suggest that the CBA4P isolate reduces levels of leptin in SJL mice, leading to lower IFN-gamma production. Therefore, the CBA4P isolate of L. acidophilus is a promising new probiotic strain for the control of Th1 inflammatory diseases.
脂肪细胞产生的瘦素会增强Th1依赖的免疫刺激和自身免疫性疾病。已知乳酸菌根据分离菌株的不同会促进或抑制Th1反应。我们研究了与C57BL/6小鼠相比，瑞士吉姆·兰伯特（SJL）小鼠对Th1依赖的免疫疾病的敏感性是否可由能够减少脂肪细胞瘦素释放的特定乳酸菌调节。从C57BL/6和SJL小鼠中分离出白色脂肪细胞，并与嗜酸乳杆菌新的CBA4P和TPA3P分离株以及鼠李糖乳杆菌9595（LR）的细菌提取物，或与经乳酸菌处理的巨噬细胞的条件培养基（CM）一起孵育。通过同基因脾淋巴细胞的代谢活性来确定经处理的脂肪细胞上清液诱导的免疫调节作用。通过酶联免疫吸附测定（ELISA）试验对脂肪细胞产生的瘦素、巨噬细胞产生的肿瘤坏死因子（TNF）-α和白细胞介素（IL）-1β以及淋巴细胞产生的IFN-γ和IL-4进行定量。结果显示，CBA4P和LR处理的脂肪细胞的上清液降低了SJL小鼠淋巴细胞的代谢活性，而与CBA4P处理的巨噬细胞的CM一起孵育的脂肪细胞对淋巴细胞没有刺激作用。这些作用与瘦素水平相关。在存在CBA4P和LR提取物的情况下，SJL小鼠的脂肪细胞产生的瘦素水平较低。当与CBA4P处理的细胞上清液一起孵育时，SJL小鼠的淋巴细胞产生的IFN-γ水平较低。这种免疫抑制作用取决于经乳酸菌处理的巨噬细胞产生的TNF-α和IL-1β水平。综上所述，这些结果表明，CBA4P分离株降低了SJL小鼠的瘦素水平，导致IFN-γ产生减少。因此，嗜酸乳杆菌的CBA4P分离株是控制Th1炎症性疾病的一种有前景的新型益生菌菌株。
