Regional production of nitric oxide after a peripheral or central low dose of LPS in mice

Mirella Zinetti, Fabio Benigni, Silvano Sacco, Manuela Minto, Grazia Galli, Sarah Salmona, Giuseppe Andreoni, Annamaria Vezzani, Pietro Ghezzi, Maddalena Fratelli

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Nitric oxide (NO) plays a key role in the pathophysiology of inflammation and sepsis. The regulation of the peripheral inducible NO synthase (iNOS - responsible for the massive NO synthesis in inflammation) has been extensively studied in sepsis, but little is known about the actual NO production and its dependence on the location of the primary stimulus (endotoxin, LPS). We measured the activation of the NO pathway after a central (intracerebroventricular) or systemic (intravenous) low dose of LPS (2.5 μg/mouse) in three ways: the accumulation of its stable end products (nitrites/nitrates) in the circulation, the induction of iNOS mRNA and the decrease in sodium nitroprusside-dependent ADP ribosylation of proteins in the liver and brain. Plasma nitrites/nitrates increased after LPS by either route. iNOS mRNA was induced in the liver after intravenous and, to a lower extent, in the brain after intracerebroventricular LPS. Ex vivo ADP ribosylation was decreased in both organs after both administration routes, although to different degrees (higher in the liver after intravenous and in the brain after intracerebroventricular administration), suggesting that NO had been produced in the periphery and in the brain after both routes of LPS administration, despite the fact that no LPS is expected to reach the brain after peripheral low-dose injection. Our data thus demonstrate a cross-talk between periphery and brain in the regulation of NO by LPS. Additionally, the possibility of iNOS-independent NO synthesis stimulated by LPS is implied by the discrepancy between the amount of local NO production suggested by ADP ribosylation and the iNOS mRNA levels.

Original languageEnglish
Pages (from-to)364-370
Number of pages7
JournalNeuroImmunoModulation
Volume3
Issue number6
Publication statusPublished - Jul 1997

Fingerprint

Nitric Oxide
Brain
Adenosine Diphosphate
Nitrites
Nitrates
Messenger RNA
Liver
Sepsis
Inflammation
Nitroprusside
Nitric Oxide Synthase Type II
Endotoxins
Injections
Proteins

Keywords

  • ADP ribosylation
  • Brain
  • Endotoxin
  • Liver
  • Nitric oxide synthases

ASJC Scopus subject areas

  • Endocrinology
  • Neuroscience(all)
  • Immunology

Cite this

Zinetti, M., Benigni, F., Sacco, S., Minto, M., Galli, G., Salmona, S., ... Fratelli, M. (1997). Regional production of nitric oxide after a peripheral or central low dose of LPS in mice. NeuroImmunoModulation, 3(6), 364-370.

Regional production of nitric oxide after a peripheral or central low dose of LPS in mice. / Zinetti, Mirella; Benigni, Fabio; Sacco, Silvano; Minto, Manuela; Galli, Grazia; Salmona, Sarah; Andreoni, Giuseppe; Vezzani, Annamaria; Ghezzi, Pietro; Fratelli, Maddalena.

In: NeuroImmunoModulation, Vol. 3, No. 6, 07.1997, p. 364-370.

Research output: Contribution to journalArticle

Zinetti, M, Benigni, F, Sacco, S, Minto, M, Galli, G, Salmona, S, Andreoni, G, Vezzani, A, Ghezzi, P & Fratelli, M 1997, 'Regional production of nitric oxide after a peripheral or central low dose of LPS in mice', NeuroImmunoModulation, vol. 3, no. 6, pp. 364-370.
Zinetti M, Benigni F, Sacco S, Minto M, Galli G, Salmona S et al. Regional production of nitric oxide after a peripheral or central low dose of LPS in mice. NeuroImmunoModulation. 1997 Jul;3(6):364-370.
Zinetti, Mirella ; Benigni, Fabio ; Sacco, Silvano ; Minto, Manuela ; Galli, Grazia ; Salmona, Sarah ; Andreoni, Giuseppe ; Vezzani, Annamaria ; Ghezzi, Pietro ; Fratelli, Maddalena. / Regional production of nitric oxide after a peripheral or central low dose of LPS in mice. In: NeuroImmunoModulation. 1997 ; Vol. 3, No. 6. pp. 364-370.
@article{ba14a066503c42e7b65377e9f3bdd24e,
title = "Regional production of nitric oxide after a peripheral or central low dose of LPS in mice",
abstract = "Nitric oxide (NO) plays a key role in the pathophysiology of inflammation and sepsis. The regulation of the peripheral inducible NO synthase (iNOS - responsible for the massive NO synthesis in inflammation) has been extensively studied in sepsis, but little is known about the actual NO production and its dependence on the location of the primary stimulus (endotoxin, LPS). We measured the activation of the NO pathway after a central (intracerebroventricular) or systemic (intravenous) low dose of LPS (2.5 μg/mouse) in three ways: the accumulation of its stable end products (nitrites/nitrates) in the circulation, the induction of iNOS mRNA and the decrease in sodium nitroprusside-dependent ADP ribosylation of proteins in the liver and brain. Plasma nitrites/nitrates increased after LPS by either route. iNOS mRNA was induced in the liver after intravenous and, to a lower extent, in the brain after intracerebroventricular LPS. Ex vivo ADP ribosylation was decreased in both organs after both administration routes, although to different degrees (higher in the liver after intravenous and in the brain after intracerebroventricular administration), suggesting that NO had been produced in the periphery and in the brain after both routes of LPS administration, despite the fact that no LPS is expected to reach the brain after peripheral low-dose injection. Our data thus demonstrate a cross-talk between periphery and brain in the regulation of NO by LPS. Additionally, the possibility of iNOS-independent NO synthesis stimulated by LPS is implied by the discrepancy between the amount of local NO production suggested by ADP ribosylation and the iNOS mRNA levels.",
keywords = "ADP ribosylation, Brain, Endotoxin, Liver, Nitric oxide synthases",
author = "Mirella Zinetti and Fabio Benigni and Silvano Sacco and Manuela Minto and Grazia Galli and Sarah Salmona and Giuseppe Andreoni and Annamaria Vezzani and Pietro Ghezzi and Maddalena Fratelli",
year = "1997",
month = "7",
language = "English",
volume = "3",
pages = "364--370",
journal = "NeuroImmunoModulation",
issn = "1021-7401",
publisher = "S. Karger AG",
number = "6",

}

TY - JOUR

T1 - Regional production of nitric oxide after a peripheral or central low dose of LPS in mice

AU - Zinetti, Mirella

AU - Benigni, Fabio

AU - Sacco, Silvano

AU - Minto, Manuela

AU - Galli, Grazia

AU - Salmona, Sarah

AU - Andreoni, Giuseppe

AU - Vezzani, Annamaria

AU - Ghezzi, Pietro

AU - Fratelli, Maddalena

PY - 1997/7

Y1 - 1997/7

N2 - Nitric oxide (NO) plays a key role in the pathophysiology of inflammation and sepsis. The regulation of the peripheral inducible NO synthase (iNOS - responsible for the massive NO synthesis in inflammation) has been extensively studied in sepsis, but little is known about the actual NO production and its dependence on the location of the primary stimulus (endotoxin, LPS). We measured the activation of the NO pathway after a central (intracerebroventricular) or systemic (intravenous) low dose of LPS (2.5 μg/mouse) in three ways: the accumulation of its stable end products (nitrites/nitrates) in the circulation, the induction of iNOS mRNA and the decrease in sodium nitroprusside-dependent ADP ribosylation of proteins in the liver and brain. Plasma nitrites/nitrates increased after LPS by either route. iNOS mRNA was induced in the liver after intravenous and, to a lower extent, in the brain after intracerebroventricular LPS. Ex vivo ADP ribosylation was decreased in both organs after both administration routes, although to different degrees (higher in the liver after intravenous and in the brain after intracerebroventricular administration), suggesting that NO had been produced in the periphery and in the brain after both routes of LPS administration, despite the fact that no LPS is expected to reach the brain after peripheral low-dose injection. Our data thus demonstrate a cross-talk between periphery and brain in the regulation of NO by LPS. Additionally, the possibility of iNOS-independent NO synthesis stimulated by LPS is implied by the discrepancy between the amount of local NO production suggested by ADP ribosylation and the iNOS mRNA levels.

AB - Nitric oxide (NO) plays a key role in the pathophysiology of inflammation and sepsis. The regulation of the peripheral inducible NO synthase (iNOS - responsible for the massive NO synthesis in inflammation) has been extensively studied in sepsis, but little is known about the actual NO production and its dependence on the location of the primary stimulus (endotoxin, LPS). We measured the activation of the NO pathway after a central (intracerebroventricular) or systemic (intravenous) low dose of LPS (2.5 μg/mouse) in three ways: the accumulation of its stable end products (nitrites/nitrates) in the circulation, the induction of iNOS mRNA and the decrease in sodium nitroprusside-dependent ADP ribosylation of proteins in the liver and brain. Plasma nitrites/nitrates increased after LPS by either route. iNOS mRNA was induced in the liver after intravenous and, to a lower extent, in the brain after intracerebroventricular LPS. Ex vivo ADP ribosylation was decreased in both organs after both administration routes, although to different degrees (higher in the liver after intravenous and in the brain after intracerebroventricular administration), suggesting that NO had been produced in the periphery and in the brain after both routes of LPS administration, despite the fact that no LPS is expected to reach the brain after peripheral low-dose injection. Our data thus demonstrate a cross-talk between periphery and brain in the regulation of NO by LPS. Additionally, the possibility of iNOS-independent NO synthesis stimulated by LPS is implied by the discrepancy between the amount of local NO production suggested by ADP ribosylation and the iNOS mRNA levels.

KW - ADP ribosylation

KW - Brain

KW - Endotoxin

KW - Liver

KW - Nitric oxide synthases

UR - http://www.scopus.com/inward/record.url?scp=12644296009&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=12644296009&partnerID=8YFLogxK

M3 - Article

VL - 3

SP - 364

EP - 370

JO - NeuroImmunoModulation

JF - NeuroImmunoModulation

SN - 1021-7401

IS - 6

ER -