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.
Highlights
Inorganic polyphosphate [poly(P)] is a linear polymer composed of tens to hundreds of orthophosphate (Pi) residues linked by highenergy phosphate bonds and widely found in organisms ranging from bacteria to mammals [1]
None of these induced inducible nitric oxide synthase (iNOS) expression alone even at 1 mM [all poly(P) concentrations are presented in terms of phosphate residues], while a marked induction of iNOS was observed in LPS-stimulated macrophages (Figure 1A)
We further showed that extracellular inorganic poly(P) reduces iNOS expression induced by LPS stimulation in mouse peritoneal macrophages
Summary
Inorganic polyphosphate [poly(P)] is a linear polymer composed of tens to hundreds of orthophosphate (Pi) residues linked by highenergy phosphate bonds and widely found in organisms ranging from bacteria to mammals [1]. Roles of poly(P) in mammals, including humans, have been revealed in the last decade. Despite the ubiquitous distribution of poly(P) in tissues and cells, including brain, heart, kidney, lung, liver, plasma, peripheral blood mononuclear cells, and mast cells [15,16,17], current knowledge pertaining to the functions of poly(P) is limited. This prompted us to further investigate the functions of poly(P)
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call