Feb 2, 2016

A novel polymorphism in nitric oxide synthase interacting protein (NOSIP) modulates nitric oxide synthesis and influences mortality in human sepsis

BioRxiv : the Preprint Server for Biology
Ratnadeep MukherjeeBalachandran Ravindran

Abstract

Nitric oxide performs a wide variety of versatile functions in the immune system. But its precise role in the pathogenesis of acute inflammation and sepsis is still controversial. In the present study, we demonstrate a novel mutation in nitric oxide synthase interacting protein (NOSIP) and its association with mortality in sepsis. We also show direct physical interaction of NOSIP with inducible nitric oxide synthase (iNOS), and demonstrate that differences in expression of NOSIP could influence differential induction of nitric oxide by monocytes/macrophages among species. Observations made in mice deficient in iNOS suggest that protective mechanism of nitric oxide in LPS induced inflammation is probably mediated by inhibiton of IL-1β; synthesis. Differential nitric oxide production between mice and humans is also reflected upon IL-1β; production between the species, where a clear inverse relationship emerges between nitric oxide and IL-1β;. Thus, our study reveals NOSIP as an important regulator of inflammation by virtue of its ability to influence nitric oxide mediated inhibition of IL-1β; synthesis and has opened up new avenues for therapeutic strategies against sepsis.

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Mentioned in this Paper

Septicemia
Gene Polymorphism
ISYNA1 gene
Study
Pathogenic Aspects
Immune System
Nitric Oxide Biosynthetic Process
Pathogenesis
Interleukin-1
Murine

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