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Sökning: WFRF:(Vesterlund Liselotte)

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1.
  • Assadi, Ghazaleh, et al. (författare)
  • Functional Analyses of the Crohn's Disease Risk Gene LACC1
  • 2016
  • Ingår i: PLOS ONE. - San Francisco, USA : Public Library of Science. - 1932-6203. ; 11:12
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Genetic variation in the Laccase (multicopper oxidoreductase) domain-containing 1 (LACC1) gene has been shown to affect the risk of Crohn's disease, leprosy and, more recently, ulcerative colitis and juvenile idiopathic arthritis. LACC1 function appears to promote fatty-acid oxidation, with concomitant inflammasome activation, reactive oxygen species production, and anti-bacterial responses in macrophages. We sought to contribute to elucidating LACC1 biological function by extensive characterization of its expression in human tissues and cells, and through preliminary analyses of the regulatory mechanisms driving such expression.Methods: We implemented Western blot, quantitative real-time PCR, immunofluorescence microscopy, and flow cytometry analyses to investigate fatty acid metabolism-immune nexus (FAMIN; the LACC1 encoded protein) expression in subcellular compartments, cell lines and relevant human tissues. Gene-set enrichment analyses were performed to initially investigate modulatory mechanisms of LACC1 expression. A small-interference RNA knockdown in vitro model system was used to study the effect of FAMIN depletion on peroxisome function.Results: FAMIN expression was detected in macrophage-differentiated THP-1 cells and several human tissues, being highest in neutrophils, monocytes/macrophages, myeloid and plasmacytoid dendritic cells among peripheral blood cells. Subcellular co-localization was exclusively confined to peroxisomes, with some additional positivity for organelle endomembrane structures. LACC1 co-expression signatures were enriched for genes involved in peroxisome proliferator-activated receptors (PPAR) signaling pathways, and PPAR ligands downregulated FAMIN expression in in vitro model systems.Conclusion: FAMIN is a peroxisome-associated protein with primary role(s) in macrophages and other immune cells, where its metabolic functions may be modulated by PPAR signaling events. However, the precise molecular mechanisms through which FAMIN exerts its biological effects in immune cells remain to be elucidated.
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2.
  • Ljotsson, Brjann, et al. (författare)
  • Internet-delivered exposure and mindfulness based therapy for irritable bowel syndrome - A randomized controlled trial
  • 2010
  • Ingår i: Behaviour Research and Therapy. - : Elsevier Science B.V., Amsterdam.. - 0005-7967 .- 1873-622X. ; 48:6, s. 531-539
  • Tidskriftsartikel (refereegranskat)abstract
    • The aim of this study was to investigate if cognitive behavior therapy (cc based on exposure and mindfulness exercises delivered via the Internet would be effective in treating participants with irritable bowel syndrome (IBS). Participants were recruited through self-referral. Eighty-six participants were included in the study and randomized to treatment or control condition (an online discussion forum). One participant was excluded after randomization. The main outcome measure was IBS-symptom severity and secondary measures included IBS-related quality of life. GI-specific anxiety, depression and general functioning. Participants were assessed at pre-treatment, post-treatment and 3 month follow-up (treatment condition only). Four participants (5% of total sample) in the treatment condition did not participate in post-treatment assessment. Participants in the treatment condition reported a 42% decrease and participants in the control group reported a 12% increase in primary IBS-symptoms. Compared to the control condition, participants in the treatment group improved on all secondary outcome measures with a large between group effect size on quality of life (Cohens d - 1.21). We conclude that CBT-based on exposure and mindfulness delivered via the Internet can be effective in treating IBS-patients, alleviating the total burden of symptoms and increasing quality of life.
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3.
  • Nilsson, Anna, et al. (författare)
  • Macrophage expression of LRP1, a receptor for apoptotic cells and unopsonized erythrocytes, can be regulated by glucocorticoids
  • 2012
  • Ingår i: Biochemical and Biophysical Research Communications - BBRC. - San Diego : Elsevier. - 0006-291X .- 1090-2104. ; 417:4, s. 1304-1309
  • Tidskriftsartikel (refereegranskat)abstract
    • Macrophage phagocytosis of apoptotic cells, or unopsonized viable CD47(-/-) red blood cells, can be mediated by the interaction between calreticulin (CRT) on the target cell and LDL receptor-related protein-1 (LRP1/CD91/alpha 2-macroglobulin receptor) on the macrophage. Glucocorticoids (GC) are powerful in treatment of a range of inflammatory conditions, and were shown to enhance macrophage uptake of apoptotic cells. Here we investigated if the ability of GC to promote macrophage uptake of apoptotic cells could in part be mediated by an upregulation of macrophage LRP1 expression. Using both resident peritoneal and bone marrow-derived macrophages, we found that the GC dexamethasone could dose- and time-dependently increase macrophage LRP1 expression. The GC receptor-inhibitor RU486 could dose-dependently prevent LRP1 upregulation. Dexamethasone-treated macrophages did also show enhanced phagocytosis of apoptotic thymocytes as well as unopsonized viable CD47(-/-) red blood cells, which was sensitive to inhibition by the LRP1-agonist RAP. In conclusion, these data suggest that GC-stimulated macrophage uptake of apoptotic cells may involve an upregulation of macrophage LRP1 expression and enhanced LRP1-mediated phagocytosis. (C) 2012 Elsevier Inc. All rights reserved.
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