Regulation of tumour necrosis factor receptor expression on neutrophils by arachidonic acid and other long chain fatty acids.
type: CreativeWork
description: Tumor necrosis factor (TNF) is a pro-inflammatory cytokine with multiple biological effects. The receptors for this cytokine on neutrophils have been shown to be rapidly down-regulated following activation, leading to the release of soluble forms of these receptors. Thus neutrophils become less responsive to TNF and the soluble TNF receptors (TNFR) serve to control TNF activity. During inflammation, leukocytes become activated as a result of the action of a variety of mediators. These mediators include not only cytokines but also lipids, such as the pro-inflammatory 00-6 fatty acid, arachidonic acid (AA) and its metabolites. Cellular activation leads to the release of AA from membrane phospholipids. AA regulates the function of many cell types including neutrophils. In view of the known pro-inflammatory properties of AA and the anti-inflammatory properties of 00-3 fatty acids, a study was undertaken to examine whether or not these fatty acids regulate the expression and release of TNFR in neutrophils. While much emphasis has been placed on agonist-induced down-regulation of TNFR, our data show that AA causes a rapid (10-20 min) and dose-dependent (0.5 to 30 uM) increase (8-fold) in the surface expression of both classes of TNFR (TNFRl and TNFRlI) on human neutrophils, at concentrations found in inflammatory fluids. This correlates with an increase in superoxide production to a TNF challenge. In contrast, both fMLP and LPS significantly reduce the expression of both TNF receptors. Interestingly, in neutrophils pretreated with AA, fMLP causes an increase in TNF receptor expression, consistent with AA preventing the fMLP-induced receptor release in neutrophil culture. In addition, while AA causes an increase in TNF receptor expression on matured HL-60 cells (neutrophil-like cells), a decrease occurs on HUVEC and non-matured HL-60 cells. These data demonstrate a unique effect of AA on neutrophils. The relationship between AA and the anti-inflammatory (0-3 fatty acids, D…
abstract: Tumor necrosis factor (TNF) is a pro-inflammatory cytokine with multiple biological effects. The receptors for this cytokine on neutrophils have been shown to be rapidly down-regulated following activation, leading to the release of soluble forms of these receptors. Thus neutrophils become less responsive to TNF and the soluble TNF receptors (TNFR) serve to control TNF activity. During inflammation, leukocytes become activated as a result of the action of a variety of mediators. These mediators include not only cytokines but also lipids, such as the pro-inflammatory 00-6 fatty acid, arachidonic acid (AA) and its metabolites. Cellular activation leads to the release of AA from membrane phospholipids. AA regulates the function of many cell types including neutrophils. In view of the known pro-inflammatory properties of AA and the anti-inflammatory properties of 00-3 fatty acids, a study was undertaken to examine whether or not these fatty acids regulate the expression and release of TNFR in neutrophils. While much emphasis has been placed on agonist-induced down-regulation of TNFR, our data show that AA causes a rapid (10-20 min) and dose-dependent (0.5 to 30 uM) increase (8-fold) in the surface expression of both classes of TNFR (TNFRl and TNFRlI) on human neutrophils, at concentrations found in inflammatory fluids. This correlates with an increase in superoxide production to a TNF challenge. In contrast, both fMLP and LPS significantly reduce the expression of both TNF receptors. Interestingly, in neutrophils pretreated with AA, fMLP causes an increase in TNF receptor expression, consistent with AA preventing the fMLP-induced receptor release in neutrophil culture. In addition, while AA causes an increase in TNF receptor expression on matured HL-60 cells (neutrophil-like cells), a decrease occurs on HUVEC and non-matured HL-60 cells. These data demonstrate a unique effect of AA on neutrophils. The relationship between AA and the anti-inflammatory (0-3 fatty acids, D…
author: Moghaddami, Fatemeh (Nahid)
keywords: neutrophils; phospholipids; fatty acids; arachidonic acid
date published: 2004
date modified: 2026-07-24T00:50:48Z
provider: University of Adelaide
publisher: Networked Digital Library of Theses and Dissertations
type: WebPage
source organization: University of Adelaide

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property ID: Handle
value: http://hdl.handle.net/2440/58487