Orally administered bovine lactoferrin induces caspase-1 and interleukin-18 in the mouse intestinal mucosa: a possible explanation for inhibition of carcinogenesis and metastasis
Orally administered bovine lactoferrin induces caspase-1 and interleukin-18 in the mouse intestinal mucosa: a possible explanation for inhibition of carcinogenesis and metastasis
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DOI：
10.1016/j.cyto.2003.09.009
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发表时间：
2004-01-07
期刊：
影响因子：
3.8
通讯作者：
Tsuda, H
中科院分区：
文献类型：
--
作者：
Iigo, M;Shimamura, M;Tsuda, H
我们先前已经证明，口服牛乳铁蛋白(BLF)显著抑制肺转移克隆的形成，这种抑制可能是由于T细胞和NK细胞的激活所致。此外，我们还发现BLF可诱导小肠上皮细胞产生IL-18。本研究旨在证实BLF对细胞因子产生的反应，并评估其潜在的机制。BLF及其胃酶水解物(BLFH)或BTF单次给药后1~3h，小肠IL-18水平显著升高。重要的是，虽然IL-18在每天服用七次BLF或bLFH后显著增加，但连续七天服用BTF几乎没有效果。除IL-18外，BLF还能显著提高小鼠小肠caspase-1活性和干扰素-γ水平(P<0.05)。同样，在腹膜巨噬细胞中，BLF显著增强caspase-1活性和IL-18水平。最后，caspase-1抑制剂在体外显著降低BLF介导的IL-18的诱导。(BTF在体外对半胱氨酸天冬氨酸氨基转移酶-1、干扰素-γ和IL-18均无影响。)这些结果表明，BLF及其水解物提高caspase-1活性可能是体内产生成熟IL-18，从而增强T细胞和NK细胞对肿瘤细胞杀伤活性的重要途径。(C)2003爱思唯尔有限公司。保留所有权利。
We have previously demonstrated that oral administration of bovine lactoferrin (bLF) markedly inhibits lung metastatic colony formation, and that this inhibition was possibly due to the activation of T and NK cells. Furthermore, we found that interleukin- 18 (IL-18) is induced in epithelial cells of the small intestine by bLF. The present study was undertaken to confirm cytokine production in response to bLF and to assess the underlying mechanisms. Markedly elevated IL-18 levels were found in the small intestine 1-3 h after a single administration of bLF, its pepsin hydrolysate (bLFH), or bTF. Importantly, while IL-18 was significantly increased after a regimen of seven daily administrations of bLF or bLFH, administration of bTF over the course of seven days had little or no effect. In addition to IL-18, a significant increase in caspase-1 activity and interferon-gamma (IFN-gamma) was found in the small intestine after administration of bLF. Similarly, in peritoneal macrophages, bLF markedly enhanced caspase-1 activity and IL-18 levels. Finally, a caspase-1 inhibitor significantly decreased bLF mediated induction of IL-18 in vitro. (bTF had no effect on either caspase-1 or IFN-gamma or on IL-18 in vitro.) These results demonstrate the possibility that elevation of caspase-1 activity by bLF and its hydrolysate may be important for production of mature IL-18 in vivo, and thus in potentiating the killing activity of T and NK cells against tumor cells. (C) 2003 Elsevier Ltd. All rights reserved.