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 journalArticlepeer-review

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

Keywords

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

ASJC Scopus subject areas

  • Endocrinology
  • Neuroscience(all)
  • Immunology

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