The capacity of foodstuffs to induce innate immune activation of human monocytes in vitro is dependent on food content of stimulants of Toll-like receptors 2 and 4
The capacity of foodstuffs to induce innate immune activation of human monocytes in vitro is dependent on food content of stimulants of Toll-like receptors 2 and 4
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DOI：
10.1017/s0007114510003004
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发表时间：
2011-01-14
影响因子：
3.6
通讯作者：
Erridge, Clett
中科院分区：
文献类型：
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作者：
Erridge, Clett
脂肪餐的摄入与人类受试者中的短暂、低度全身性炎症反应相关，涉及循环单核细胞的活化和促炎细胞因子的分泌。然而，目前尚不清楚不同的食物如何促进炎症信号。在对来自普通食品的40种过滤灭菌的可溶性提取物的筛选中，发现7种在体外诱导人单核细胞分泌TNF-α和IL-6。为了研究什么可以区分炎性和非炎性食物提取物，Toll样受体（TLR）2和TLR 4的刺激物使用转染有每个TLR的人胚肾-293细胞进行定量，并使用定义的细菌脂肽（BLP）和脂多糖（LPS）标准进行校准。这些测定显示，虽然大多数食物含有不可检测水平的TLR 2或TLR 4刺激物，但所有TNF-α诱导食物在可溶性和不溶性部分中都含有TLR 2（高达1100 ng BLP当量/g）或TLR 4（高达2700 ng LPS当量/g）的刺激物。TLR兴奋剂主要存在于肉制品和加工食品中，但在新鲜水果和蔬菜中很少或检测不到。食物提取物诱导单核细胞分泌TNF-α的能力与TLR 2（r 0.837）和TLR 4刺激物（r 0.748）的含量相关，并通过特异性抑制TLR 2和TLR 4完全消除。发现LPS和BLP对典型的烹饪时间和温度、低pH和蛋白酶处理具有高度抗性。总之，显然未变质的食物可以含有大量的TLR 2和TLR 4的刺激物，这两者都可以调节它们刺激炎症信号的能力。
The ingestion of fatty meals is associated with a transient, low-grade systemic inflammatory response in human subjects, involving the activation of circulating monocytes and the secretion of pro-inflammatory cytokines. However, it is not yet clear how different foodstuffs may promote inflammatory signalling. In a screen of forty filter-sterilised soluble extracts from common foodstuffs, seven were found to induce the secretion of TNF-alpha and IL-6 from human monocytes in vitro. To investigate what may differentiate inflammatory from noninflammatory food extracts, stimulants of Toll-like receptor (TLR) 2 and TLR4 were quantified using human embryonic kidney-293 cells transfected with each TLR, and calibrated with defined bacterial lipopeptide (BLP) and lipopolysaccharide (LPS) standards. These assays revealed that while most foods contained undetectable levels of TLR2 or TLR4 stimulants, all TNF-alpha-inducing foods contained stimulants of either TLR2 (up to 1100 ng BLP-equivalent/g) or TLR4 (up to 2700 ng LPS-equivalent/g) in both the soluble and insoluble fractions. TLR stimulants were present mainly in meat products and processed foods, but were minimal or undetectable in fresh fruit and vegetables. The capacity of food extracts to induce TNF-alpha secretion in monocytes correlated with the content of both TLR2 (r 0.837) and TLR4 stimulants (r 0.748), and was completely abolished by specific inhibition of TLR2 and TLR4. LPS and BLP were found to be highly resistant to typical cooking times and temperatures, low pH and protease treatment. In conclusion, apparently unspoiled foodstuffs can contain large quantities of stimulants of TLR2 and TLR4, both of which may regulate their capacity to stimulate inflammatory signalling.