A novel lipid a from halomonas magadiensis inhibits enteric lPS-induced human monocyte activation

P. Maffia, A. Ialenti, P. Di Meglio, G. Grassia, M. Di Rosa, R. Lanzetta, A. Molinaro, A. Silipo, W. Grant, A. Ianaro

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

Lipopolysaccharide (LPS) endotoxin is the bacterial product responsible for the clinical syndrome of Gram-negative septicemia and endotoxic shock. During sepsis, microbial antigens, such as LPS, activate monocytes and macrophages to produce several pro-inflammatory cytokines, among which tumor necrosis factor- (TNF-) appears to be very important for the development of endotoxic shock. The endotoxic properties of LPS principally reside in the lipid A (LIP A) component, which is the primary immunostimulatory center of Gram-negative bacteria. In recent years there has been a continuous effort to identify molecules able to antagonize the deleterious effects of endotoxic shock. In this study we show that a novel LIP A fraction from the LPS of Halomonas magadiensis (Hm), a Gram-negative extremophilic and alkaliphilic bacterium, significantly inhibits the synthesis of TNF- by human monocytes activated by Escherichia coli LPS. LIP A from Hm exerts these effects by interfering with E. coli LPS for activation of Toll-like receptor 4 expressed in human cells. This result defines Hm LIP A as a novel class of LPS antagonist whose structural features could be utilized for the design of compounds for the treatment of Gram-negative sepsis.

LanguageEnglish
Pages354-360
Number of pages7
JournalEuropean Journal of Immunology
Volume36
DOIs
Publication statusPublished - 2006

Fingerprint

Halomonas
Lipopolysaccharides
Monocytes
Lipids
Septic Shock
Sepsis
Lipid A
Escherichia coli
Toll-Like Receptor 4
Gram-Negative Bacteria
Endotoxins
Tumor Necrosis Factor-alpha
Macrophages
Cytokines
Bacteria
Antigens

Keywords

  • halomonas magadiensis
  • toll-like receptor 4
  • TNF-ALPHA
  • Lipid A
  • monocytes

Cite this

Maffia, P., Ialenti, A., Di Meglio, P., Grassia, G., Di Rosa, M., Lanzetta, R., ... Ianaro, A. (2006). A novel lipid a from halomonas magadiensis inhibits enteric lPS-induced human monocyte activation. European Journal of Immunology, 36, 354-360. https://doi.org/10.1002/eji.200535305
Maffia, P. ; Ialenti, A. ; Di Meglio, P. ; Grassia, G. ; Di Rosa, M. ; Lanzetta, R. ; Molinaro, A. ; Silipo, A. ; Grant, W. ; Ianaro, A. / A novel lipid a from halomonas magadiensis inhibits enteric lPS-induced human monocyte activation. In: European Journal of Immunology. 2006 ; Vol. 36. pp. 354-360.
@article{efb365771738411db9c1dc7c38508f38,
title = "A novel lipid a from halomonas magadiensis inhibits enteric lPS-induced human monocyte activation",
abstract = "Lipopolysaccharide (LPS) endotoxin is the bacterial product responsible for the clinical syndrome of Gram-negative septicemia and endotoxic shock. During sepsis, microbial antigens, such as LPS, activate monocytes and macrophages to produce several pro-inflammatory cytokines, among which tumor necrosis factor- (TNF-) appears to be very important for the development of endotoxic shock. The endotoxic properties of LPS principally reside in the lipid A (LIP A) component, which is the primary immunostimulatory center of Gram-negative bacteria. In recent years there has been a continuous effort to identify molecules able to antagonize the deleterious effects of endotoxic shock. In this study we show that a novel LIP A fraction from the LPS of Halomonas magadiensis (Hm), a Gram-negative extremophilic and alkaliphilic bacterium, significantly inhibits the synthesis of TNF- by human monocytes activated by Escherichia coli LPS. LIP A from Hm exerts these effects by interfering with E. coli LPS for activation of Toll-like receptor 4 expressed in human cells. This result defines Hm LIP A as a novel class of LPS antagonist whose structural features could be utilized for the design of compounds for the treatment of Gram-negative sepsis.",
keywords = "halomonas magadiensis, toll-like receptor 4, TNF-ALPHA, Lipid A, monocytes",
author = "P. Maffia and A. Ialenti and {Di Meglio}, P. and G. Grassia and {Di Rosa}, M. and R. Lanzetta and A. Molinaro and A. Silipo and W. Grant and A. Ianaro",
year = "2006",
doi = "10.1002/eji.200535305",
language = "English",
volume = "36",
pages = "354--360",
journal = "European Journal of Immunology",
issn = "0014-2980",

}

Maffia, P, Ialenti, A, Di Meglio, P, Grassia, G, Di Rosa, M, Lanzetta, R, Molinaro, A, Silipo, A, Grant, W & Ianaro, A 2006, 'A novel lipid a from halomonas magadiensis inhibits enteric lPS-induced human monocyte activation' European Journal of Immunology, vol. 36, pp. 354-360. https://doi.org/10.1002/eji.200535305

A novel lipid a from halomonas magadiensis inhibits enteric lPS-induced human monocyte activation. / Maffia, P.; Ialenti, A.; Di Meglio, P.; Grassia, G.; Di Rosa, M.; Lanzetta, R.; Molinaro, A.; Silipo, A.; Grant, W.; Ianaro, A.

In: European Journal of Immunology, Vol. 36, 2006, p. 354-360.

Research output: Contribution to journalArticle

TY - JOUR

T1 - A novel lipid a from halomonas magadiensis inhibits enteric lPS-induced human monocyte activation

AU - Maffia, P.

AU - Ialenti, A.

AU - Di Meglio, P.

AU - Grassia, G.

AU - Di Rosa, M.

AU - Lanzetta, R.

AU - Molinaro, A.

AU - Silipo, A.

AU - Grant, W.

AU - Ianaro, A.

PY - 2006

Y1 - 2006

N2 - Lipopolysaccharide (LPS) endotoxin is the bacterial product responsible for the clinical syndrome of Gram-negative septicemia and endotoxic shock. During sepsis, microbial antigens, such as LPS, activate monocytes and macrophages to produce several pro-inflammatory cytokines, among which tumor necrosis factor- (TNF-) appears to be very important for the development of endotoxic shock. The endotoxic properties of LPS principally reside in the lipid A (LIP A) component, which is the primary immunostimulatory center of Gram-negative bacteria. In recent years there has been a continuous effort to identify molecules able to antagonize the deleterious effects of endotoxic shock. In this study we show that a novel LIP A fraction from the LPS of Halomonas magadiensis (Hm), a Gram-negative extremophilic and alkaliphilic bacterium, significantly inhibits the synthesis of TNF- by human monocytes activated by Escherichia coli LPS. LIP A from Hm exerts these effects by interfering with E. coli LPS for activation of Toll-like receptor 4 expressed in human cells. This result defines Hm LIP A as a novel class of LPS antagonist whose structural features could be utilized for the design of compounds for the treatment of Gram-negative sepsis.

AB - Lipopolysaccharide (LPS) endotoxin is the bacterial product responsible for the clinical syndrome of Gram-negative septicemia and endotoxic shock. During sepsis, microbial antigens, such as LPS, activate monocytes and macrophages to produce several pro-inflammatory cytokines, among which tumor necrosis factor- (TNF-) appears to be very important for the development of endotoxic shock. The endotoxic properties of LPS principally reside in the lipid A (LIP A) component, which is the primary immunostimulatory center of Gram-negative bacteria. In recent years there has been a continuous effort to identify molecules able to antagonize the deleterious effects of endotoxic shock. In this study we show that a novel LIP A fraction from the LPS of Halomonas magadiensis (Hm), a Gram-negative extremophilic and alkaliphilic bacterium, significantly inhibits the synthesis of TNF- by human monocytes activated by Escherichia coli LPS. LIP A from Hm exerts these effects by interfering with E. coli LPS for activation of Toll-like receptor 4 expressed in human cells. This result defines Hm LIP A as a novel class of LPS antagonist whose structural features could be utilized for the design of compounds for the treatment of Gram-negative sepsis.

KW - halomonas magadiensis

KW - toll-like receptor 4

KW - TNF-ALPHA

KW - Lipid A

KW - monocytes

UR - http://dx.doi.org/10.1002/eji.200535305

U2 - 10.1002/eji.200535305

DO - 10.1002/eji.200535305

M3 - Article

VL - 36

SP - 354

EP - 360

JO - European Journal of Immunology

T2 - European Journal of Immunology

JF - European Journal of Immunology

SN - 0014-2980

ER -