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- Jennbacken, Karin, 1978, et al.
(författare)
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Glucose impairs B-1 cell function in diabetes.
- 2013
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Ingår i: Clinical and experimental immunology. - : Oxford University Press (OUP). - 1365-2249 .- 0009-9104. ; 174:1, s. 129-38
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Tidskriftsartikel (refereegranskat)abstract
- B-1 lymphocytes produce natural immunoglobulin (Ig)M, among which a large proportion is directed against apoptotic cells and altered self-antigens, such as modified low-density lipoprotein (LDL). Thereby, natural IgM maintains homeostasis in the body and is also protective against atherosclerosis. Diabetic patients have an increased risk of developing certain infections as well as atherosclerosis compared with healthy subjects, but the underlying reason is not known. The aim of this study was to investigate whether diabetes and insulin resistance affects B-1 lymphocytes and their production of natural IgM. We found that diabetic db/db mice had lower levels of peritoneal B-1a cells in the steady state-condition compared to controls. Also, activation of B-1 cells with the Toll-like receptor (TLR)-4 agonist Kdo2-Lipid A or immunization against Streptococcus pneumoniae led to a blunted IgM response in the diabetic db/db mice. In-vitro experiments with isolated B-1 cells showed that high concentrations of glucose, but not insulin or leptin, caused a reduced secretion of total IgM and copper-oxidized (CuOx)-LDL- and malondialdehyde (MDA)-LDL-specific IgM from B-1 cells in addition to a decreased differentiation into antibody-producing cells, proliferation arrest and increased apoptosis. These results suggest that metabolic regulation of B-1 cells is of importance for the understanding of the role of this cell type in life-style-related conditions.
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- Staffas, Anna, 1982, et al.
(författare)
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Upregulation of Flt3 is a passive event in Hoxa9/Meis1-induced acute myeloid leukemia in mice.
- 2017
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Ingår i: Oncogene. - : Springer Science and Business Media LLC. - 1476-5594 .- 0950-9232. ; 36, s. 1516-1524
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Tidskriftsartikel (refereegranskat)abstract
- HOXA9, MEIS1 and FLT3 are genes frequently upregulated in human acute myeloid leukemia. Hoxa9 and Meis1 also cooperate to induce aggressive AML with high Flt3 expression in mice, suggesting an important role for Flt3 in Hoxa9/Meis1-induced leukemogenesis. To define the role of Flt3 in AML with high Hoxa9/Meis1, we treated mice with Hoxa9/Meis1-induced AML with the Flt3 inhibitor AC220, used an Flt3-ligand (FL-/-) knockout model, and investigated whether overexpression of Flt3 could induce leukemia together with overexpression of Hoxa9. Flt3 inhibition by AC220 did not delay AML development in mice transplanted with bone marrow cells overexpressing Hoxa9 and Meis1. In addition, Hoxa9/Meis1 cells induced AML in FL-/- mice as rapid as in wild-type mice. However, FL-/- mice had reduced organ infiltration compared with wild-type mice, suggesting some Flt3-dependent effect on leukemic invasiveness. Interestingly, leukemic Hoxa9/Meis1 cells from sick mice expressed high levels of Flt3 regardless of presence of its ligand, showing that Flt3 is a passive marker on these cells. In line with this, combined engineered overexpression of Flt3 and Hoxa9 did not accelerate the progression to AML. We conclude that the Hoxa9- and Meis1-associated upregulation of Flt3 is not a requirement for leukemic progression induced by Hoxa9 and Meis1.Oncogene advance online publication, 12 September 2016; doi:10.1038/onc.2016.318.
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- Svahn, Sara L, et al.
(författare)
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Dietary Omega-3 Fatty Acids Increase Survival and Decrease Bacterial Load in Mice Subjected to Staphylococcus aureus-Induced Sepsis
- 2016
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Ingår i: Infection and Immunity. - : American Society for Microbiology. - 0019-9567 .- 1098-5522. ; 84:4, s. 1205-1213
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Tidskriftsartikel (refereegranskat)abstract
- Sepsis caused by Staphylococcus aureus is increasing in incidence. With the alarming use of antibiotics, S. aureus is prone to become methicillin resistant. Antibiotics are the only widely used pharmacological treatment for sepsis. Interestingly, mice fed high-fat diet (HFD) rich in polyunsaturated fatty acids have better survival of S. aureus-induced sepsis than mice fed HFD rich in saturated fatty acids (HFD-S). To investigate what component of polyunsaturated fatty acids, i.e., omega-3 or omega-6 fatty acids, exerts beneficial effects on the survival of S. aureus-induced sepsis, mice were fed HFD rich in omega-3 or omega-6 fatty acids for 8 weeks prior to inoculation with S. aureus. Further, mice fed HFD-S were treated with omega-3 fatty acid metabolites known as resolvins. Mice fed HFD rich in omega-3 fatty acids had increased survival and decreased bacterial loads compared to those for mice fed HFD-S after S. aureus-induced sepsis. Furthermore, the bacterial load was decreased in resolvin-treated mice fed HFD-S after S. aureus-induced sepsis compared with that in mice treated with vehicle. Dietary omega-3 fatty acids increase the survival of S. aureus-induced sepsis by reversing the deleterious effect of HFD-S on mouse survival.
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