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- Mattsson Hultén, Lillemor, 1951, et al.
(författare)
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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
- 1998
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Ingår i: Transplantation. - 0041-1337. ; 66:3, s. 364-9
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Tidskriftsartikel (refereegranskat)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.
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| 2. |
- Mattsson Hultén, Lillemor, 1951, et al.
(författare)
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Oxysterols present in atherosclerotic tissue decrease the expression of lipoprotein lipase messenger RNA in human monocyte-derived macrophages.
- 1996
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Ingår i: The Journal of clinical investigation. - 0021-9738. ; 97:2, s. 461-8
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Tidskriftsartikel (refereegranskat)abstract
- The presence of oxysterols in macrophages isolated from atherosclerotic tissue and the effect of oxysterols on the regulation of lipoprotein lipase (LPL) mRNA were studied. Both rabbit and human macrophages, freshly isolated from atherosclerotic aorta, show about the same distribution of oxysterols, analyzed by isotope dilution mass spectrometry, except that all three preparations of human arterial-derived macrophages contained high levels of 27-hydroxycholesterol, which was not found in rabbit macrophages. To determine if oxysterols regulate LPL expression, human monocyte-derived macrophages were incubated with different oxysterols. Incubation with 7 beta-hydroxycholesterol and 25-hydroxycholesterol resulted in a 70-75% reduction of LPL mRNA, analyzed by quantitative RT-PCR. Cholesterol and other tested oxysterols showed no effect on macrophage LPL mRNA expression compared with control. LPL activity in the medium was also reduced after exposure of the macrophages to 7 beta-hydroxycholesterol and 25-hydroxycholesterol. In conclusion, we have demonstrated accumulation of oxysterols in macrophage-derived foam cells isolated from atherosclerotic aorta. There was suppression of LPL mRNA in human monocyte-derived macrophages after incubation with 7 beta-hydroxycholesterol and 25-hydroxycholesterol. It is tempting to suggest that an exposure to oxysterols may explain our earlier observation of a low level of LPL mRNA in arterial foam cells.
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