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首页> 外文期刊>Life sciences >Effects of tiludronate and ibandronate on the secretion of proinflammatory cytokines and nitric oxide from macrophages in vitro.
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Effects of tiludronate and ibandronate on the secretion of proinflammatory cytokines and nitric oxide from macrophages in vitro.

机译：替洛膦酸和伊班膦酸对体外巨噬细胞促炎细胞因子和一氧化氮分泌的影响。

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Bisphosphonates inhibit osteoclastic bone resorption and are used for the treatment of bone diseases. Some bisphosphonates, such as clodronate and tiludronate, can be incorporated into non-hydrolysable ATP analogues in cells, whereas the more potent anti-resorptive aminoalkylbisphosphonates are not metabolised. Furthermore, clodronate inhibits proinflammatory cytokine and nitric oxide (NO) secretion from activated macrophages in vitro and has anti-inflammatory properties in vivo, especially when delivered into cells by liposomes. By contrast, aminobisphosphonates can induce an acute phase response and fever in vivo, which appears to involve the induction of cytokine secretion. In this study we examined the effect of liposome-mediated intracellular delivery of one aminobisphosphonate, ibandronate, and one metabolizable bisphosphonate, tiludronate, on the secretion of inflammatory mediators. The intracellular uptake of bisphosphonates by macrophages was enhanced by a factor of 20-200 by using liposomes. Tiludronate dose-dependently inhibited both cytokine and NO secretion from activated macrophages, and liposomal tiludronate was more potent than the free drug. By contrast, ibandronate enhanced LPS-induced secretion of IL-1beta and IL-6 but did not affect TNFalpha or NO secretion at non-cytotoxic concentrations. The present results, together with our previous studies, strongly suggest that bisphosphonates can be grouped into those that are metabolised by cells and that are capable of inhibiting cytokine and NO secretion from macrophages, thus having potential anti-inflammatory properties, and those that are not metabolised but can actually enhance the production of cytokines following macrophage activation.
机译：双膦酸盐抑制破骨细胞的骨吸收，并用于治疗骨疾病。可以将某些双膦酸盐（例如氯膦酸盐和替洛膦酸盐）掺入细胞中不可水解的ATP类似物中，而更有效的抗吸收性氨基烷基双膦酸盐则不被代谢。此外，氯膦酸盐在体外抑制活化的巨噬细胞的促炎性细胞因子和一氧化氮（NO）分泌，并且在体内具有抗炎特性，尤其是当通过脂质体传递到细胞中时。相比之下，氨基双膦酸酯可在体内引起急性期反应和发烧，这似乎涉及对细胞因子分泌的诱导。在这项研究中，我们检查了脂质体介导的一种氨基双膦酸盐伊班膦酸盐和一种可代谢的双膦酸盐替丁膦酸盐对炎性介质分泌的影响。通过使用脂质体，巨噬细胞对双膦酸盐的细胞内摄取提高了20-200倍。替鲁膦酸盐剂量依赖性地抑制活化巨噬细胞的细胞因子和NO分泌，并且替洛膦酸脂质体比游离药物更有效。相比之下，伊班膦酸盐可增强LPS诱导的IL-1beta和IL-6分泌，但在非细胞毒性浓度下不会影响TNFalpha或NO分泌。目前的结果以及我们以前的研究强烈表明，双膦酸盐可以归类为那些被细胞代谢的，能够抑制巨噬细胞分泌细胞因子和NO从而具有潜在的抗炎特性的双膦酸盐，而那些不是代谢，但实际上可以增强巨噬细胞激活后细胞因子的产生。

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