title: Inorganic polyphosphate suppresses lipopolysaccharide-induced inducible nitric oxide synthase (iNOS) expression in macrophages.
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.
authors.affiliation: Department of Advanced Prosthodontics, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
authors.forename: Kana
authors.initials: K
authors.lastname: Harada
authors.forename: Toshikazu
authors.initials: T
authors.lastname: Shiba
authors.forename: Kazuya
authors.initials: K
authors.lastname: Doi
authors.forename: Koji
authors.initials: K
authors.lastname: Morita
authors.forename: Takayasu
authors.initials: T
authors.lastname: Kubo
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Makihara
authors.forename: Adriano
authors.initials: A
authors.lastname: Piattelli
authors.forename: Yasumasa
authors.initials: Y
authors.lastname: Akagawa
mesh_terms: D000818:Animals; D002470:Cell Survival; D002473:Cell Wall / Q000378:metabolism; D015536:Down-Regulation; D007113:Immunity, Innate; D007249:Inflammation; D008070:Lipopolysaccharides / Q000737:chemistry*; D008264:Macrophages / Q000378:metabolism*; D017737:Macrophages, Peritoneal / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009569:Nitric Oxide / Q000737:chemistry; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism*; D009573:Nitrites / Q000737:chemistry; D010710:Phosphates / Q000737:chemistry*; D011122:Polyphosphates / Q000737:chemistry; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D008070:Lipopolysaccharides; D009573:Nitrites; D010710:Phosphates; D011122:Polyphosphates; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse
references.citation: Haematologica. 2006 Sep;91(9):1180-6
references.pmid: 16956816
references.citation: J Biol Chem. 2004 Oct 22;279(43):44250-7
references.pmid: 15308650
references.citation: Nat Commun. 2013;4:1362
references.pmid: 23322050
references.citation: Int J Biol Sci. 2008 Feb 03;4(1):37-47
references.pmid: 18274622
references.citation: J Biol Chem. 2006 Oct 20;281(42):31337-47
references.pmid: 16923814
references.citation: Blood. 2008 Oct 1;112(7):2810-6
references.pmid: 18544683
references.citation: Biochem Biophys Res Commun. 2004 Feb 13;314(3):695-703
references.pmid: 14741691
references.citation: Cell. 2009 Dec 11;139(6):1143-56
references.pmid: 20005807
references.citation: Nat Immunol. 2010 May;11(5):373-84
references.pmid: 20404851
references.citation: Annu Rev Biochem. 2009;78:605-47
references.pmid: 19344251
references.citation: PLoS One. 2011;6(8):e23278
references.pmid: 21858054
references.citation: Immunity. 2011 May 27;34(5):637-50
references.pmid: 21616434
references.citation: Proc Natl Acad Sci U S A. 2006 Jan 24;103(4):903-8
references.pmid: 16410357
references.citation: Cell Calcium. 2011 Aug;50(2):113-9
references.pmid: 21752464
references.citation: J Neurosci. 2007 Jun 13;27(24):6500-9
references.pmid: 17567811
references.citation: J Leukoc Biol. 2011 Jun;89(6):873-91
references.pmid: 21233414
references.citation: J Biol Chem. 2010 Mar 26;285(13):9420-9428
references.pmid: 20124409
references.citation: PLoS One. 2009;4(4):e5404
references.pmid: 19404398
references.citation: Int Rev Immunol. 2011 Feb;30(1):16-34
references.pmid: 21235323
references.citation: Nitric Oxide. 2010 Sep 15;23(2):75-93
references.pmid: 20438856
references.citation: Proc Natl Acad Sci U S A. 2003 Sep 30;100(20):11249-54
references.pmid: 12970465
references.citation: J Dent Res. 2004 Aug;83(8):613-8
references.pmid: 15271969
references.citation: J Bone Miner Res. 1998 May;13(5):803-12
references.pmid: 9610744
references.citation: Blood. 2010 May 13;115(19):3980-8
references.pmid: 20228273
references.citation: J Biol Chem. 1995 Mar 17;270(11):5818-22
references.pmid: 7890711
references.citation: J Biol Chem. 2003 Jul 18;278(29):26788-92
references.pmid: 12740373
references.citation: Blood. 2011 Dec 22;118(26):6963-70
references.pmid: 21976677
references.citation: J Biol Chem. 2012 Aug 17;287(34):28435-44
references.pmid: 22761438