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

Kana Harada1, Toshikazu Shiba, Kazuya Doi

  • 1Department of Advanced Prosthodontics, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.

Plos One
|September 17, 2013
PubMed

Insights

Inorganic polyphosphate (poly(P)) suppresses nitric oxide (NO) production in macrophages by reducing inducible nitric oxide synthase (iNOS) mRNA expression. Longer poly(P) chains show greater suppression, suggesting a role in regulating innate immunity.

Area of Science:

  • Immunology
  • Molecular Biology
  • Biochemistry

Background:

  • Macrophages are key immune cells that produce inflammatory mediators like nitric oxide (NO) to combat pathogens.
  • Overproduction of inflammatory mediators can harm host tissues, necessitating tight regulatory mechanisms.
  • Inorganic polyphosphate (poly(P)) is a ubiquitous cellular polymer found in mammalian cells.

Purpose of the Study:

  • To investigate the effect of inorganic polyphosphate (poly(P)) on the expression of inducible nitric oxide synthase (iNOS) in macrophages.
  • To determine the role of poly(P) in regulating nitric oxide (NO) production in response to bacterial components.
  • To elucidate the molecular mechanism by which poly(P) influences inflammatory mediator production.

Main Methods:

  • Primary mouse peritoneal macrophages were stimulated with lipopolysaccharide (LPS).
  • The effect of varying chain lengths of poly(P) on iNOS expression and NO release was assessed.
  • iNOS mRNA levels were quantified using molecular biology techniques.
  • Tumor Necrosis Factor (TNF) release was measured to assess specificity.

Main Results:

  • Poly(P) significantly suppressed LPS-induced iNOS expression in macrophages.
  • Suppression of iNOS expression by poly(P) was dependent on poly(P) chain length, with longer chains being more potent.
  • Poly(P) reduced LPS-induced NO release and iNOS mRNA expression, indicating regulation at the transcriptional level.
  • Poly(P) did not affect LPS-induced TNF release, suggesting a specific modulation of iNOS.

Conclusions:

  • Inorganic polyphosphate (poly(P)) acts as a negative regulator of inducible nitric oxide synthase (iNOS) expression in macrophages.
  • Poly(P) modulates innate immunity by down-regulating NO production at the mRNA level.
  • The chain length of poly(P) influences its potency in suppressing iNOS expression, highlighting a potential therapeutic target.

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