Modulation of the cytokine responses in equine macrophages following TACE-inhibition.
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.
Wijnker
Joris J
JJ
Department of Equine Sciences, Faculty of Veterinary Medicine, Utrecht University, Yalelaan 12, 3584 CM Utrecht, The Netherlands.
Bull
Sarah
S
Van Dijk
Paul
P
Veenman
Janine N
JN
Rutten
Victor P
VP
Klein
Wim R
WR
Fink-Gremmels
Johanna
J
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
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