Panahipour Layla, Kochergina Evgeniya, Kreissl Alexandra, Haiden Nadja, Gruber Reinhard
Department of Oral Biology, Medical University of Vienna, Sensengasse 2a, 1090 Vienna, Austria.
Department of Paediatrics and Adolescent Medicine, Division of Neonatology, Medical University of Vienna, Währingergürtel 18-20, 1090 Vienna, Austria.
Cytokine X. 2019 May 25;1(2):100009. doi: 10.1016/j.cytox.2019.100009. eCollection 2019 Jun.
Milk holds an anti-inflammatory response that is particularly important to protecting infants against necrotizing enterocolitis. Milk might also exert anti-inflammatory effects in adulthood, including the oral cavity where macrophages of the oral mucosal control innate immunity defense. It remains unknown, however, whether milk can modulate the local inflammatory response by affecting the polarization of macrophages.
To determine whether pasteurized human milk and pasteurized cow milk can provoke macrophage polarization, murine bone marrow macrophages and RAW264.7 cells were exposed to human saliva or the inflammatory cytokines IL1β and TNFα. Activation of pro-(M1) inflammatory response is indicated by the expression of IL1 and IL8. To determine polarization towards a M2 phenotype, the expression of arginase 1 (ARG1) and chitinase-like 3 (Chil3) was determined by reverse transcriptase PCR and immunoassay. Western blot was done on phosphorylated p38 and JNK.
Aqueous fractions of human milk and cow milk from different donors, respectively, significantly decreased the inflammatory response of primary macrophages and RAW264.7 cells when exposed to saliva or IL1 and TNFα. Similar to IL4, human milk and cow milk caused a robust expression of ARG1 and Chil3 in primary macrophages. The polarization of macrophages by pasteurized milk occurred independent of the phosphorylation of p38 and JNK.
These data suggest that pasteurized milk, independent of the origin, can cause the polarization of macrophages from a pro-inflammatory M1 towards a pro-resolving M2 phenotype. Thus, milk might have a protective role for the oral cavity by modulation of the macrophage-based innate immune system.
牛奶具有抗炎反应，这对保护婴儿免受坏死性小肠结肠炎的侵害尤为重要。牛奶在成年期可能也会发挥抗炎作用，包括在口腔中，口腔黏膜巨噬细胞控制着先天免疫防御。然而，牛奶是否能通过影响巨噬细胞的极化来调节局部炎症反应仍不清楚。
为了确定巴氏杀菌的人乳和巴氏杀菌的牛乳是否能引发巨噬细胞极化，将小鼠骨髓巨噬细胞和RAW264.7细胞暴露于人唾液或炎性细胞因子IL1β和TNFα中。IL1和IL8的表达表明促炎（M1）反应的激活。为了确定向M2表型的极化，通过逆转录聚合酶链反应和免疫测定法测定精氨酸酶1（ARG1）和几丁质酶样3（Chil3）的表达。对磷酸化的p38和JNK进行蛋白质印迹分析。
来自不同供体的人乳和牛乳的水相部分，在暴露于唾液或IL1和TNFα时，分别显著降低了原代巨噬细胞和RAW264.7细胞的炎症反应。与IL4相似，人乳和牛乳在原代巨噬细胞中引起了ARG1和Chil3的强烈表达。巴氏杀菌牛奶引起的巨噬细胞极化与p38和JNK的磷酸化无关。
这些数据表明，无论来源如何，巴氏杀菌牛奶都能使巨噬细胞从促炎的M1型向促解决的M2型极化。因此，牛奶可能通过调节基于巨噬细胞的先天免疫系统对口腔起到保护作用。
