RT Journal Article
SR Electronic
T1 A novel polymorphism in nitric oxide synthase interacting protein (NOSIP) modulates nitric oxide synthesis and influences mortality in human sepsis
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 038398
DO 10.1101/038398
A1 Ratnadeep Mukherjee
A1 Diwakar Kumar Singh
A1 Pijus Kanti Barman
A1 Birendra Kumar Prusty
A1 Pravat Thatoi
A1 Rina Tripathy
A1 Bidyut Kumar Das
A1 Balachandran Ravindran
YR 2016
UL http://biorxiv.org/content/early/2016/02/02/038398.abstract
AB Nitric oxide performs a wide variety of versatile functions in the immune system. But it’s 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.