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- Alvarado-Kristensson, Maria, et al.
(författare)
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p38-MAPK signals survival by phosphorylation of caspase-8 and caspase-3 in human neutrophils
- 2004
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Ingår i: Journal of Experimental Medicine. - : Rockefeller University Press. - 0022-1007 .- 1540-9538. ; 199:4, s. 449-458
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Tidskriftsartikel (refereegranskat)abstract
- Neutrophil apoptosis occurs both in the bloodstream and in the tissue and is considered essential for the resolution of an inflammatory process. Here, we show that p38-mitogen-activated protein kinase (MAPK) associates to caspase-8 and caspase-3 during neutrophil apoptosis and that p38-MAPK activity, previously shown to be a survival signal in these primary cells, correlates with the levels of caspase-8 and caspase-3 phosphorylation. In in vitro experiments, immunoprecipitated active p38-MAPK phosphorylated and inhibited the activity of the active p20 subunits of caspase-8 and caspase-3. Phosphopeptide mapping revealed that these phosphorylations occurred on serine-364 and serine-150, respectively. Introduction of mutated (S150A), but not wild-type, TAT-tagged caspase-3 into primary neutrophils made the Fas-induced apoptotic response insensitive to p38-MAPK inhibition. Consequently, p38-MAPK can directly phosphorylate and inhibit the activities of caspase-8 and caspase-3 and thereby hinder neutrophil apoptosis, and, in so doing, regulate the inflammatory response.
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- Alvarado-Kristensson, Maria, et al.
(författare)
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p38 Mitogen-activated protein kinase and phosphatidylinositol 3-kinase activities have opposite effects on human neutrophil apoptosis.
- 2002
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Ingår i: FASEB Journal. - : Wiley. - 1530-6860 .- 0892-6638. ; 16:1, s. 31-129
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Tidskriftsartikel (refereegranskat)abstract
- Neutrophil apoptosis is essential for resolution of inflammatory reactions. Here, we studied the role of two apoptosis/survival-associated protein kinases in this process. We discovered a previously undetected early and transient inhibition of the activity of p38 mitogen-activated protein kinase (p38 MAPK) during both spontaneous and Fas-induced apoptosis. Pharmacological inhibition of this enzyme augmented the activation of caspases and the apoptotic response, which suggests that the p38 MAPK signals survival in neutrophils. Our finding that caspase-3 activity was initiated during the transient inhibition of p38 MAPK suggests that apoptosis is initiated during this inhibition. Furthermore, such transient inhibition was counteracted by granulocyte-macrophage colony-stimulating factor, which elicits survival. We also found that neither this inhibition of p38 MAPK nor the spontaneous apoptotic response depended on Fas. Instead, the early inhibition of p38 MAPK concurred with a Fas-induced activation of phosphatidylinositol 3-kinase, inhibition of which reduced apoptosis. Thus, the Fas-induced augmentation of spontaneous apoptosis can be explained by its activation of phosphatidylinositol 3-kinase. We conclude that p38 MAPK activity represents a survival signal that is inactivated transiently during both spontaneous and Fas-induced apoptosis, whereas Fas-induced phosphatidylinositol 3-kinase activity is a proapoptotic signal in isolated human neutrophils.
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- Andersson, Gunvor, et al.
(författare)
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Barns vardagsliv i familjehem
- 2001
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Ingår i: Barns vardag i det senmoderna samhället. - 9127084132
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Bokkapitel (övrigt vetenskapligt/konstnärligt)
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- Andersson, Gunvor, et al.
(författare)
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Haverier i social barnavård? Fem fallstudier
- 2001
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Bok (övrigt vetenskapligt/konstnärligt)abstract
- HAVERIER i social barnavård är lyckligtvis mycket ovanliga. I detta arbete analyseras fem fall som alla vid någon tidpunkt har utvecklats på ett olyckligt sätt. De olika fallen ger tillsammans en bred belysning av dilemmor och möjligheter i socialt och psykiatriskt arbete med utsatta barn. Genom att analysera olika vändpunkter i fallen diskuteras både haverier och god praktik. Läsaren kan själv ta ställning: Vad är ett haveri? Hur kan haverier undvikas? Det finns också rikligt med stoff för debatt kring barnets bästa, barns rättigheter, och mediernas och allmänhetens ansvar. Boken har alla förutsättningar att engagera både den intresserade allmänheten och journalister, liksom personer under utbildning eller fortbildning vid socialhögskolor, psykiatriutbildningar och jurist- eller polishögskolor. FALLSTUDIEN som metod har varit av avgörande betydelse inom hjärnforskningen och annan medicinsk forskning. Inom samhällsvetenskaperna har den däremot varit försummad. I denna bok illustreras olika angreppssätt genom fem olika typer av fall. Dessutom presenteras teori kring fallstudier och berättande, liksom metodiska synpunkter på fallstudien som forsknings- och utredningsmetod.
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