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Butylated hydroxytoluene and N-acetylcysteine attenuates tumor necrosis factor-alpha (TNF-alpha) secretion and TNF-alpha mRNA expression in alveolar macrophages from human lung transplant recipients in vitro

Författare och institution:
Lillemor Mattsson Hultén (Wallenberglaboratoriet); Helena Lindmark (Institutionen för invärtesmedicin); Henrik Scherstén (Hjärt-kärlinstitutionen); Olov Wiklund (Institutionen för invärtesmedicin); Folke Nilsson (Hjärt-kärlinstitutionen); Gerdt C. Riise (Institutionen för invärtesmedicin)
Publicerad i:
Transplantation, 66 ( 3 ) s. 364-9
0041-1337 (Print)
Artikel, refereegranskad vetenskaplig
Sammanfattning (abstract):
BACKGROUND: Tumor necrosis factor-alpha (TNF-alpha) is a polypeptide cytokine principally produced by macrophages/monocytes and commonly associated with inflammatory conditions. The present study was designed to investigate whether the antioxidants butylated hydroxytoluene (BHT) and N-acetylcysteine (NAC) modified TNF-alpha production in stimulated and unstimulated alveolar macrophages from lung transplant recipients in vitro. METHODS: The effects of BHT and NAC on TNF-alpha production were studied both with and without lipopolysaccharide (LPS) activation of alveolar macrophages from bronchoalveolar lavage fluid. TNF-alpha was quantitated in cell culture medium using an enzyme-linked immunosorbent assay. TNF-alpha mRNA expression was analyzed by quantitative reverse transcription-polymerase chain reaction on total RNA extracted from the incubated alveolar macrophages. RESULTS: In unstimulated alveolar macrophages, TNF-alpha levels were significantly reduced by incubation with BHT or NAC. When alveolar macrophages from patients with cytomegalovirus infection were incubated with BHT, TNF-alpha secretion was significantly lowered. A significant reduction of TNF-alpha levels in LPS-stimulated alveolar macrophages was obtained in the presence of BHT or NAC. Our data from quantitative reverse transcription-polymerase chain reaction showed that the observed decrease in protein levels of TNF-alpha was associated with a decrease in TNF-alpha mRNA expression. CONCLUSIONS: Our results indicate that antioxidant treatment may be an effective step to lower the inflammatory process caused by cytomegalovirus infection or in endotoxin (LPS)-activated macrophages. The therapeutic use of antioxidant compounds could, therefore, be of interest in conditions such as lung transplantation, in which oxidative stress and inflammation can contribute significantly to the loss of allograft function.
Ämne (baseras på Högskoleverkets indelning av forskningsämnen):
Klinisk medicin ->
Dermatologi och venereologi
Acetylcysteine/*pharmacology, Adult, Antioxidants/*pharmacology, Butylated Hydroxytoluene/*pharmacology, Female, Gene Expression/drug effects, Graft Survival/drug effects/immunology, Heart Transplantation/*immunology, Heart-Lung Transplantation/*immunology, Humans, Lipopolysaccharides/immunology, Macrophage Activation/drug effects/immunology, Macrophages, Alveolar/*drug effects/immunology, Male, Middle Aged, RNA, Messenger/genetics, Tumor Necrosis Factor-alpha/genetics/*metabolism
Postens nummer:
Posten skapad:
2007-09-05 10:41
Posten ändrad:
2011-01-20 10:00

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