title: Modulation of the cytokine responses in equine macrophages following TACE-inhibition.
abstract: The detrimental effects of the pro-inflammatory cytokine TNF-alpha during equine acute abdominal disease are well known. Its pivotal role in many human diseases has led to various in-depth studies regarding its release mechanism, in particular by TNF-alpha converting enzyme (TACE). In this study we investigated the inhibitory effect of a TACE-inhibitor on cytokine release (TNF-alpha, IL-1alpha and IL-6) in three different cell models, including U937 cells, a recently established equine macrophage cell line, known as eCAS, and primary equine PBMC. The aim was to show the similarity of TNF-alpha release through the TACE mechanism in human and equine cells after stimulation with LPS. Results indicate that, by using a TACE-inhibitor, TNF-alpha, IL-1alpha and IL-6 release can be reduced in both equine cell models and achieved comparable results in the human U937 cells. These results suggest that equine TNF-alpha, like its human homologue, is released from its membrane-bound position by TACE.
authors.affiliation: Department of Equine Sciences, Faculty of Veterinary Medicine, Utrecht University, Yalelaan 12, 3584 CM Utrecht, The Netherlands.
authors.forename: Joris J
authors.initials: JJ
authors.lastname: Wijnker
authors.forename: Sarah
authors.initials: S
authors.lastname: Bull
authors.forename: Paul
authors.initials: P
authors.lastname: Van Dijk
authors.forename: Janine N
authors.initials: JN
authors.lastname: Veenman
authors.forename: Victor P
authors.initials: VP
authors.lastname: Rutten
authors.forename: Wim R
authors.initials: WR
authors.lastname: Klein
authors.forename: Johanna
authors.initials: J
authors.lastname: Fink-Gremmels
mesh_terms: D051722:ADAM Proteins; D000072198:ADAM17 Protein; D000006:Abdomen, Acute / Q000276:immunology / Q000662:veterinary*; D000818:Animals; D016207:Cytokines / Q000276:immunology*; D005663:Furans / Q000494:pharmacology; D006734:Horse Diseases / Q000276:immunology*; D006736:Horses; D006801:Humans; D008070:Lipopolysaccharides / Q000276:immunology; D008262:Macrophage Activation / Q000276:immunology; D008264:Macrophages / Q000276:immunology*; D008666:Metalloendopeptidases / Q000276:immunology*; D011480:Protease Inhibitors / Q000494:pharmacology; D011498:Protein Precursors / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology; D020298:U937 Cells
chemical_list: D016207:Cytokines; D005663:Furans; D008070:Lipopolysaccharides; D011480:Protease Inhibitors; D011498:Protein Precursors; D014409:Tumor Necrosis Factor-alpha; C061153:tumor necrosis factor precursor; D051722:ADAM Proteins; D008666:Metalloendopeptidases; D000072198:ADAM17 Protein; C000606462:ADAM17 protein, human