並列タイトル等無機のポリリン酸はリポ多糖がマクロファージに引き起こす炎症反応を増強する
一般注記Inorganic polyphosphate (polyP) is a linear polymer of orthophosphate units that are linked by phosphoanhydride bonds and is involved in various pathophysiological processes. However, the role of polyP in immune cell dysfunction is not well-understood. In this study, using several biochemical and cell biology approaches, including cytokine assays, immunofluorescence microscopy, receptor-binding assays with quartz crystal microbalance, and dynamic light scanning, we investigated the effect of polyP on in vitro lipopolysaccharide (LPS)- induced macrophage inflammatory response. PolyP up-regulated LPS-induced production of the inflammatory cytokines, such as tumor necrosis factor , interleukin-1, and interleukin-6, in macrophages, and the effect was polyP dose– and chain length– dependent. However, orthophosphate did not exhibit this effect. PolyP enhanced the LPS-induced intracellular macrophage inflammatory signals. Affinity analysis revealed that polyP interacts with LPS, inducing formation of small micelles, and the polyP-LPS complex enhanced the binding affinity of LPS to Toll-like receptor 4 (TLR4) on macrophages. These results suggest that inorganic polyP plays a critical role in promoting inflammatory response by enhancing the interaction between LPS and TLR4 in macrophages.
Journal of Biological Chemistry. 2020, 295(12), 4014-4023.
新大院博(医)甲第968号
元資料の権利情報 : 【○!C】 2020 Ito et al. Published under exclusive license by The American Society for Biochemistry and Molecular Biology, Inc. This is an open access article under the CC BY-NC-SA license (https://creativecommons.org/licenses/by-nc-sa/4.0/).
DOIinfo:doi/10.1074/jbc.RA119.011763
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