Regulation of pentraxin-3 by antioxidants

A L Hill, D A Lowes, N R Webster, C C Sheth, N A R Gow, H F Galley

Research output: Contribution to journalArticle

17 Citations (Scopus)
3 Downloads (Pure)

Abstract

Pentraxin-3 (PTX3) may be a useful biomarker in sepsis, but its regulatory mechanisms are still unclear. Oxidative stress is well defined in patients with sepsis and has a role in regulation of inflammatory pathways which may include PTX3. We undertook an in vitro study of the effect of antioxidants on regulation of PTX3 in endothelial cells combined with a prospective observational pilot study of PTX3 in relation to markers of antioxidant capacity and oxidative stress in patients with sepsis.

Human endothelial cells were cultured with lipopolysaccharide 2 mu g ml(-1), peptidoglycan G 20 mu g ml(-1), tumour necrosis factor (TNF) alpha 10 ng ml(-1), interleukin-1 (IL-1) beta 20 ng ml(-1), or killed Candida albicans yeast cells plus either N-acetylcysteine (NAC) 25 mM, trolox 100 mM, or idebenone 1 mu M. Plasma samples were obtained from 15 patients with sepsis and 11 healthy volunteers.

PTX3 levels in plasma were higher in patients with sepsis than in healthy people [26 (1-202) ng ml(-1) compared with 6 (1-12) ng ml(-1), P=0.01]. Antioxidant capacity was lower in patients with sepsis than healthy controls [0.99 (0.1-1.7) mM compared with 2.2 (1.3-3.3) mM, P=0.01]. In patients with sepsis, lipid hydroperoxide levels were 3.32 (0.3-10.6) nM and undetectable in controls. We found no relationship between PTX3 and antioxidant capacity or lipid hydroperoxides. Cell expression of PTX3 increased with all inflammatory stimulants but was highest in cells treated with TNF alpha plus IL-1 beta. PTX3 concentrations were lower in cells co-treated with antioxidants (all P < 0.05), associated with lower nuclear factor kappa B expression for NAC and trolox (P < 0.05).

PTX3 expression is down-regulated in vitro by antioxidants. Plasma levels of PTX3 are elevated in sepsis but seem to be unrelated to markers of oxidant stress or antioxidant capacity.

Original languageEnglish
Pages (from-to)833-839
Number of pages7
JournalBritish Journal of Anaesthesia
Volume103
Issue number6
Early online date28 Oct 2009
DOIs
Publication statusPublished - Dec 2009

Keywords

  • immune response
  • infection
  • bacterial
  • fungal
  • metabolism
  • protein
  • acute phase
  • critically-ill patients
  • C-reactive protein
  • Kappa-B activation
  • candida-albicans
  • endothelial-cells
  • septic shock
  • inducible expression
  • innate immunity
  • PTX3
  • sepsis
  • infection, bacterial
  • infection, fungal
  • metabolism, protein, acute phase

Cite this

Regulation of pentraxin-3 by antioxidants. / Hill, A L; Lowes, D A; Webster, N R; Sheth, C C; Gow, N A R; Galley, H F.

In: British Journal of Anaesthesia, Vol. 103, No. 6, 12.2009, p. 833-839.

Research output: Contribution to journalArticle

Hill, AL, Lowes, DA, Webster, NR, Sheth, CC, Gow, NAR & Galley, HF 2009, 'Regulation of pentraxin-3 by antioxidants', British Journal of Anaesthesia, vol. 103, no. 6, pp. 833-839. https://doi.org/10.1093/bja/aep298
Hill, A L ; Lowes, D A ; Webster, N R ; Sheth, C C ; Gow, N A R ; Galley, H F. / Regulation of pentraxin-3 by antioxidants. In: British Journal of Anaesthesia. 2009 ; Vol. 103, No. 6. pp. 833-839.
@article{e71fe867ee914ab780de6a17c4aadac8,
title = "Regulation of pentraxin-3 by antioxidants",
abstract = "Pentraxin-3 (PTX3) may be a useful biomarker in sepsis, but its regulatory mechanisms are still unclear. Oxidative stress is well defined in patients with sepsis and has a role in regulation of inflammatory pathways which may include PTX3. We undertook an in vitro study of the effect of antioxidants on regulation of PTX3 in endothelial cells combined with a prospective observational pilot study of PTX3 in relation to markers of antioxidant capacity and oxidative stress in patients with sepsis.Human endothelial cells were cultured with lipopolysaccharide 2 mu g ml(-1), peptidoglycan G 20 mu g ml(-1), tumour necrosis factor (TNF) alpha 10 ng ml(-1), interleukin-1 (IL-1) beta 20 ng ml(-1), or killed Candida albicans yeast cells plus either N-acetylcysteine (NAC) 25 mM, trolox 100 mM, or idebenone 1 mu M. Plasma samples were obtained from 15 patients with sepsis and 11 healthy volunteers.PTX3 levels in plasma were higher in patients with sepsis than in healthy people [26 (1-202) ng ml(-1) compared with 6 (1-12) ng ml(-1), P=0.01]. Antioxidant capacity was lower in patients with sepsis than healthy controls [0.99 (0.1-1.7) mM compared with 2.2 (1.3-3.3) mM, P=0.01]. In patients with sepsis, lipid hydroperoxide levels were 3.32 (0.3-10.6) nM and undetectable in controls. We found no relationship between PTX3 and antioxidant capacity or lipid hydroperoxides. Cell expression of PTX3 increased with all inflammatory stimulants but was highest in cells treated with TNF alpha plus IL-1 beta. PTX3 concentrations were lower in cells co-treated with antioxidants (all P < 0.05), associated with lower nuclear factor kappa B expression for NAC and trolox (P < 0.05).PTX3 expression is down-regulated in vitro by antioxidants. Plasma levels of PTX3 are elevated in sepsis but seem to be unrelated to markers of oxidant stress or antioxidant capacity.",
keywords = "immune response, infection, bacterial, fungal, metabolism, protein, acute phase, critically-ill patients, C-reactive protein, Kappa-B activation, candida-albicans, endothelial-cells, septic shock, inducible expression, innate immunity, PTX3, sepsis, infection, bacterial, infection, fungal, metabolism, protein, acute phase",
author = "Hill, {A L} and Lowes, {D A} and Webster, {N R} and Sheth, {C C} and Gow, {N A R} and Galley, {H F}",
year = "2009",
month = "12",
doi = "10.1093/bja/aep298",
language = "English",
volume = "103",
pages = "833--839",
journal = "British Journal of Anaesthesia",
issn = "0007-0912",
publisher = "ELSEVIER APPL SCI PUBL LTD",
number = "6",

}

TY - JOUR

T1 - Regulation of pentraxin-3 by antioxidants

AU - Hill, A L

AU - Lowes, D A

AU - Webster, N R

AU - Sheth, C C

AU - Gow, N A R

AU - Galley, H F

PY - 2009/12

Y1 - 2009/12

N2 - Pentraxin-3 (PTX3) may be a useful biomarker in sepsis, but its regulatory mechanisms are still unclear. Oxidative stress is well defined in patients with sepsis and has a role in regulation of inflammatory pathways which may include PTX3. We undertook an in vitro study of the effect of antioxidants on regulation of PTX3 in endothelial cells combined with a prospective observational pilot study of PTX3 in relation to markers of antioxidant capacity and oxidative stress in patients with sepsis.Human endothelial cells were cultured with lipopolysaccharide 2 mu g ml(-1), peptidoglycan G 20 mu g ml(-1), tumour necrosis factor (TNF) alpha 10 ng ml(-1), interleukin-1 (IL-1) beta 20 ng ml(-1), or killed Candida albicans yeast cells plus either N-acetylcysteine (NAC) 25 mM, trolox 100 mM, or idebenone 1 mu M. Plasma samples were obtained from 15 patients with sepsis and 11 healthy volunteers.PTX3 levels in plasma were higher in patients with sepsis than in healthy people [26 (1-202) ng ml(-1) compared with 6 (1-12) ng ml(-1), P=0.01]. Antioxidant capacity was lower in patients with sepsis than healthy controls [0.99 (0.1-1.7) mM compared with 2.2 (1.3-3.3) mM, P=0.01]. In patients with sepsis, lipid hydroperoxide levels were 3.32 (0.3-10.6) nM and undetectable in controls. We found no relationship between PTX3 and antioxidant capacity or lipid hydroperoxides. Cell expression of PTX3 increased with all inflammatory stimulants but was highest in cells treated with TNF alpha plus IL-1 beta. PTX3 concentrations were lower in cells co-treated with antioxidants (all P < 0.05), associated with lower nuclear factor kappa B expression for NAC and trolox (P < 0.05).PTX3 expression is down-regulated in vitro by antioxidants. Plasma levels of PTX3 are elevated in sepsis but seem to be unrelated to markers of oxidant stress or antioxidant capacity.

AB - Pentraxin-3 (PTX3) may be a useful biomarker in sepsis, but its regulatory mechanisms are still unclear. Oxidative stress is well defined in patients with sepsis and has a role in regulation of inflammatory pathways which may include PTX3. We undertook an in vitro study of the effect of antioxidants on regulation of PTX3 in endothelial cells combined with a prospective observational pilot study of PTX3 in relation to markers of antioxidant capacity and oxidative stress in patients with sepsis.Human endothelial cells were cultured with lipopolysaccharide 2 mu g ml(-1), peptidoglycan G 20 mu g ml(-1), tumour necrosis factor (TNF) alpha 10 ng ml(-1), interleukin-1 (IL-1) beta 20 ng ml(-1), or killed Candida albicans yeast cells plus either N-acetylcysteine (NAC) 25 mM, trolox 100 mM, or idebenone 1 mu M. Plasma samples were obtained from 15 patients with sepsis and 11 healthy volunteers.PTX3 levels in plasma were higher in patients with sepsis than in healthy people [26 (1-202) ng ml(-1) compared with 6 (1-12) ng ml(-1), P=0.01]. Antioxidant capacity was lower in patients with sepsis than healthy controls [0.99 (0.1-1.7) mM compared with 2.2 (1.3-3.3) mM, P=0.01]. In patients with sepsis, lipid hydroperoxide levels were 3.32 (0.3-10.6) nM and undetectable in controls. We found no relationship between PTX3 and antioxidant capacity or lipid hydroperoxides. Cell expression of PTX3 increased with all inflammatory stimulants but was highest in cells treated with TNF alpha plus IL-1 beta. PTX3 concentrations were lower in cells co-treated with antioxidants (all P < 0.05), associated with lower nuclear factor kappa B expression for NAC and trolox (P < 0.05).PTX3 expression is down-regulated in vitro by antioxidants. Plasma levels of PTX3 are elevated in sepsis but seem to be unrelated to markers of oxidant stress or antioxidant capacity.

KW - immune response

KW - infection

KW - bacterial

KW - fungal

KW - metabolism

KW - protein

KW - acute phase

KW - critically-ill patients

KW - C-reactive protein

KW - Kappa-B activation

KW - candida-albicans

KW - endothelial-cells

KW - septic shock

KW - inducible expression

KW - innate immunity

KW - PTX3

KW - sepsis

KW - infection, bacterial

KW - infection, fungal

KW - metabolism, protein, acute phase

U2 - 10.1093/bja/aep298

DO - 10.1093/bja/aep298

M3 - Article

VL - 103

SP - 833

EP - 839

JO - British Journal of Anaesthesia

JF - British Journal of Anaesthesia

SN - 0007-0912

IS - 6

ER -