In vitro effects of poly(ADP-ribose) polymerase inhibitors on the production of tumor necrosis factor-α by interferon- γ - and lipopolysaccharide-stimulated peripheral blood mononuclear cells of horses
| Autor: | Mirella L. Meyer-Ficca, Louise L. Southwood, Luigi Bertolotti, Cristina Cacciolatti, Laura Zarucco, Ralph G. Meyer |
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| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
Lipopolysaccharides
inflammation model Lipopolysaccharide TNF⍶ In Vitro Techniques Poly(ADP-ribose) Polymerase Inhibitors Peripheral blood mononuclear cell Poly (ADP-Ribose) Polymerase Inhibitor chemistry.chemical_compound Interferon-gamma PARP1 Interferon γ PJ34 Animals Horses Tumor necrosis factor α PARP inhibitors equine Inflammation General Veterinary Tumor Necrosis Factor-alpha General Medicine PARP inhibitors PJ34 TNF⍶ equine inflammation model Molecular biology In vitro Disease Models Animal chemistry Leukocytes Mononuclear Tumor necrosis factor alpha Horse Diseases Poly(ADP-ribose) Polymerases |
| Popis: | OBJECTIVE To evaluate effects of poly(ADP-ribose) polymerase-1 (PARP1) inhibitors on the production of tumor necrosis factor-α (TNF-α) by interferon-γ (IFN-γ)– and lipopolysaccharide (LPS)-stimulated peripheral blood mononuclear cells (PBMCs) of horses as an in vitro model of inflammation in horses. SAMPLE 1,440 samples of PBMCs from 6 healthy research horses. PROCEDURES From heparinized whole blood samples, PBMC cultures were obtained. An initial dose-response trial on 48 PBMC samples from 2 horses (24 samples each) was used to determine concentrations of IFN-γ and LPS for use as low- and high-level stimulation concentrations. Seventy-two PBMC samples from 6 horses were assigned equally to 1 of 4 PARP1 inhibition categories: no PARP1 inhibitor (PARP1 inhibition control); 2-((R)-2-methylpyrrolidin-2-yl)-1H-benzimidazole-4-carbozamide dihydrochloride (ABT888);4-(3-(1-(cyclopropanecarbonyl)piperazine-4-carbonyl)-4-fluorobenzyl)phthalazin-1(2H)-one (AZD2281); or N-(6-oxo-5,6-dihydrophenanthridin-2-yl) -N,N-dimethylacetamide hydrochloride (PJ34). Samples of PBMCs from each horse and each PARP1 inhibition category were then assigned to 1 of 3 levels of IFN-γ and LPS stimulation: none (control), low stimulation, or high stimulation. After a 24-hour incubation period, a TNF-α ELISA was used to measure TNF-α concentration in the supernatant. Results were compared across treatments and for each horse. Data were analyzed with repeated-measures ANOVA. RESULTS Median TNF-α concentration was significantly lower for PJ34-treated, high-level stimulated PBMCs than for PARP1 inhibition control, high-level stimulated PBMCs; however, no other meaningful differences in TNF-α concentration were detected among the inhibition and stimulation combinations. CONCLUSIONS AND CLINICAL RELEVANCE Findings suggested that PJ34 PARP1 inhibition may reduce TNF-α production in horses, a potential benefit in reducing inflammation and endotoxin-induced damage in horses. |
| Databáze: | OpenAIRE |
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