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J Biol Chem. 2020 Mar 20;295(12):4014-4023. doi: 10.1074/jbc.RA119.011763. Epub 2020 Feb 10.

Inorganic polyphosphate potentiates lipopolysaccharide-induced macrophage inflammatory response.

Author information

1
Division of Clinical Nephrology and Rheumatology, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachi-dori, Niigata 951-8510, Japan.
2
Division of Clinical Nephrology and Rheumatology, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachi-dori, Niigata 951-8510, Japan yamamots@med.niigata-u.ac.jp.
3
Institute for Protein Research, Osaka University, Yamadaoka 3-2, Suita, Osaka 565-0871, Japan.

Abstract

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 α, interleukin-1β, 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.

KEYWORDS:

LPS micelle formation; infection; inflammation; inflammatory response; lipopolysaccharide (LPS); macrophage; micelle; polyphosphate

PMID:
32041779
PMCID:
PMC7086024
[Available on 2021-03-20]
DOI:
10.1074/jbc.RA119.011763

Conflict of interest statement

The authors declare that they have no conflicts of interest with the contents of this article.

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