Plant Sterols Increased IL-6 and TNF-α Secretion from Macrophages, but to a Lesser Extent than Cholesterol
Plant Sterols Increased IL-6 and TNF-α Secretion from Macrophages, but to a Lesser Extent than Cholesterol
复制标题
DOI：
10.5551/jat.6999
复制
发表时间：
2011-01-01
影响因子：
4.4
通讯作者：
Tsukamoto, Kazuhisa
中科院分区：
文献类型：
--
作者：
Kurano, Makoto;Iso-O, Naoyuki;Tsukamoto, Kazuhisa
目的：植物类固醇血症是一种遗传性疾病，以高胆固醇血症和过早的动脉粥样硬化为特征，在某些情况下伴有炎症状态的增加。然而，植物类固醇血症中动脉粥样硬化形成的潜在机制尚未完全阐明。方法：将RAW264.7细胞(RAW)和小鼠腹腔巨噬细胞(MPM)分别与谷甾醇(Sito)、油菜籽甾醇(Camp)和胆固醇(Chol)在低浓度(8mM、16mM)和高浓度(160mM)下孵育，观察其对脂多糖(LPS)诱导的IL-6和TNF-α分泌的影响。我们还分析了它们对两种细胞内质网(ER)应激的影响，以及对RAW细胞增殖的影响。结果：在较低的甾醇浓度下，只有Chol才有增加MPM分泌TNF-a的趋势。在高浓度时，Chol可显著增加两种细胞的肿瘤坏死因子-α的分泌，但Sito对肿瘤坏死因子-α的分泌无显著影响。Sito对IL-6分泌的影响也明显小于Chol。CAMP可增加MPM分泌的两种细胞因子，但增加幅度不如CHOL明显。结论：与胆固醇相比，植物甾醇对巨噬细胞的炎症反应和毒性较轻，提示植物甾醇本身可能不是植物类固醇血症动脉粥样硬化形成的主要原因。
Aim: Phytosterolemia is an inherited disorder characterized by hypercholesterolemia and premature atherosclerosis, together with increased inflammatory states in some cases. The underlying mechanisms of atherogenesis in phytosterolemia, however, have not been completely elucidated. In this study, we investigated whether phytosterols would affect inflammatory reactions in macrophages and macrophage cell lines.Methods: We incubated RAW264.7 cells (RAW) and mouse peritoneal macrophages (MPMs) with sitosterol (Sito), campesterol (Camp) or cholesterol (Chol) at low (8 mu M, 16 mu M) or high (160 mu M) concentrations, and investigated their effects on LPS-induced secretion of IL-6 and TNF-alpha. We also analyzed their effects on endoplasmic reticulum (ER) stress in both cells, and on the cell proliferation of RAW.Results: At low sterol concentrations, only Chol resulted in a tendency toward the increased secretion of TNF-a from MPMs. At high concentrations, Chol induced a significant increase in TNF-alpha secretions from both cells; however, Sito resulted in a non-significant increase in TNF-alpha secretion. The effects on IL-6 secretions of Sito were also significantly less than those of Chol. Camp increased the secretions of both cytokines from MPMs; however, the extent of these increases was less pronounced than that of Chol. Augmentation of ER stress was greatest with Chol among the sterols, and the proliferation of RAW cells was inhibited only with Chol.Conclusion: The lesser degree of inflammatory reactions and toxicity in macrophages with phytosterols than with cholesterol suggests that plant sterols themselves might not be primarily responsible for atherogenesis in phytosterolemia.