Inorganic polyphosphate suppresses lipopolysaccharide-induced inducible nitric oxide synthase (iNOS) expression in macrophages

PLoS One. 2013 Sep 9;8(9):e74650. doi: 10.1371/journal.pone.0074650. eCollection 2013.

Abstract

In response to infection, macrophages produce a series of inflammatory mediators, including nitric oxide (NO), to eliminate pathogens. The production of these molecules is tightly regulated via various mechanisms, as excessive responses are often detrimental to host tissues. Here, we report that inorganic polyphosphate [poly(P)], a linear polymer of orthophosphate ubiquitously found in mammalian cells, suppresses inducible nitric oxide synthase (iNOS) expression induced by lipopolysaccharide (LPS), a cell wall component of Gram-negative bacteria, in mouse peritoneal macrophages. Poly(P) with longer chains is more potent than those with shorter chains in suppressing LPS-induced iNOS expression. In addition, poly(P) decreased LPS-induced NO release. Moreover, poly(P) suppressed iNOS mRNA expression induced by LPS stimulation, thereby indicating that poly(P) reduces LPS-induced iNOS expression by down-regulation at the mRNA level. In contrast, poly(P) did not affect the LPS-induced release of TNF, another inflammatory mediator. Poly(P) may serve as a regulatory factor of innate immunity by modulating iNOS expression in macrophages.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Survival
  • Cell Wall / metabolism
  • Down-Regulation
  • Immunity, Innate
  • Inflammation
  • Lipopolysaccharides / chemistry*
  • Macrophages / metabolism*
  • Macrophages, Peritoneal / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Nitric Oxide / chemistry
  • Nitric Oxide Synthase Type II / metabolism*
  • Nitrites / chemistry
  • Phosphates / chemistry*
  • Polyphosphates / chemistry
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Lipopolysaccharides
  • Nitrites
  • Phosphates
  • Polyphosphates
  • Tumor Necrosis Factor-alpha
  • Nitric Oxide
  • Nitric Oxide Synthase Type II
  • Nos2 protein, mouse

Grants and funding

This study was supported by a Grant-in-Aid for Scientific Research (No. 23890134) from Japan Society for the Promotion of Science. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.