Some features of this site may not work without it. Date: Time: In the present work, we have focused the studies on monocyte derived DCs. The maturation signal results in several functional and phenotypic changes in the DCs. In this thesis, we have studied the influence of apoptotic cells and pro-inflammatory cytokines in their capacity to induce DC maturation and inhibit HIV-1 replication.
We, furthermore, studied the effect of proteasome inhibitors on HIV-1 replication in primary cells.Fb20 engine
We found that both the cellular and supernatant fractions of apoptotic activated peripheral blood mononuclear cells PBMC were involved in triggering DC maturation. We also found multiple signaling pathways and transcription factors being activated in DCs when they were co-cultured with ApoAct. In addition, we also demonstrated that proteasome inhibitors can effectively reduce transcription from the HIV-1 LTR-promoter. The results were similar when the PBMCs were treated with proteasome inhibitors alone or in combination with other antiretroviral drugs.
In conclusion, we have showed that activated apoptotic lymphocytes and pro- inflammatory mediators can induce maturation in DCs and reduce HIV-1 infection, at least in part by inducing APOBEC3 molecules.
Some features of this site may not work without it. Date: Time: Abstract The invariant natural killer T iNKT cells are a subset of T lymphocytes that share characteristics of both innate and adaptive immunity. These cells are defined as T cells restricted by the lipid antigen presenting molecule CD1d and express an invariant T cell receptor TCR as well as classical natural killer NK cell markers.
Upon stimulation iNKT cells rapidly produce large amounts of cytokines and chemokines and activate various other cell types including NK cells and dendritic cells DCs. In addition they are involved in the immune responses against tumors and in regulating autoimmune and inflammatory diseases. Several viruses have been shown to evade human iNKT cell responses by down- regulating CD1d expression in infected cells. The mechanism behind CD1d down-regulation was dependent on inhibition of CD1d recycling, and interaction between CD1d and Vpu in early endosomal compartments.
Vpu down-regulates different host-proteins involved in innate immunity. Interestingly, down-regulation of CD1d and CD4 was found to occur by distinct mechanisms. Collectively, these findings suggest that the Vpu protein of HIV-1 may play a significant role in evasion from CD1d-specific immune responses, and moreover support the notion that iNKT cells play an important role in the host defence against HIV In addition to recognition of exogenous lipid antigens presented by CD1d, iNKT cells can be activated by cytokine or surface receptor stimulation with or without presentation of endogenous lipids.
These alternative pathways for iNKT cell activation may be particularly important in settings where target cells express no or low levels of CD1d, such as transformed or virus infected cells.
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In summary, the work presented in this thesis expands our knowledge about how iNKT cells respond to target cells and how viruses work to counteract such recognition. List of papers: I. Markus Moll, Sofia K. Inhibition of lipid antigen presentation in dendritic cells by HIV-1 Vpu interference with CD1d recycling from endosomal compartments. Blood Sep 16; 11 : Fulltext DOI.
Institution: Karolinska Institutet. Supervisor: Moll, Markus. Publication year: Statistics Total Visits Views Invariant Search DSpace. This Collection. United States.
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Number of Planned Food Mfg. Projects Continues Slide It indicates that capital investment in facility projects may be subdued for the rest of Supply Chain. Supply Chains Challenged to Innovate by Virus As we work toward stabilization of the global supply chain, technology and innovation will be required ingredients to enable a swift rebound.
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Education in laboratory animal science is compulsory for those who intend to work and conduct research with laboratory animals at Karolinska Institutet. The aim of these CPD Continuing professional development is to follow the legal requirements for maintenance and demonstration of competence,…. Lectures and seminars. This course is intended for those of you who would like and introduction to Office and Microsoft Teams. Intern kurs och fortbildning. Training in Excel in Swedish on 18 August at This course is intended for those of you who would like to become more efficient when working with Excel.
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This course is intended for those of you who would like to become more efficient when working with Outlook. Title on thesis: "Models of the lung tissue microenvironment for studies of human myeloid cell function". Campus Syd, Medicin, Huddinge. Dissertation: Lorenzo Baronti. Training in Word in Swedish on 24 August at This course is intended for those of you who would like to use smart functions and become more efficient when working with Word. Emerging Topics in Artificial Intelligence.
Some features of this site may not work without it. Novel aspects of metabolic regulation and inflammation in human adipocytes Author: Pettersson, Annie. Date: Time: Abstract The significance of adipose tissue and obesity has been recognized in numerous pathologies. However, the mechanisms behind this connection are not yet completely understood. Our overall hypothesis was that these factors may influence metabolism and inflammation in human white adipose tissue WAT.
In paper I, we studied the effects of LXR activation on human basal lipolysis. We demonstrate that hormone-sensitive lipase HSL and perilipin 1 PLIN1two proteins important for lipolysis, are downregulated on both mRNA and protein level by GW treatment, which changes the morphology of the lipid droplet coating.
MAFB mRNA expression was upregulated in obesity and downregulated after weight loss in adipose tissue from four different human cohorts. In turn, knockdown of MAFB in adipocytes resulted in reduced expression of pro-inflammatory factors. MAFB was mainly expressed in adipose tissue macrophages and its expression correlated positively with macrophage- and pro-inflammatory markers in WAT, and negatively with insulin-stimulated lipogenesis and stimulated lipolysis in human mature adipocytes, suggesting that it might be involved in the development of unhealthy glucose- and lipid metabolism.
Both basal and insulin-stimulated glucose uptake were inhibited by SIK inhibitor.
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Taken together, SIK2 may have a protective role in obesity-induced loss of insulin sensitivity. In summary, we have identified the roles of three factors in human adipocytes, all of which were previously uncharacterised in human WAT. We show that LXR enhances spontaneous lipolysis while inhibiting insulin-stimulated glucose uptake in human adipocytes, two features associated with an unfavourable metabolic profile. Finally, we demonstrate that MAFB is itself a regulator of inflammation in human adipocytes and that SIK2 positively regulates glucose uptake in human adipocytes.
Our findings contribute to the understanding of the metabolic syndrome and its development in obesity. List of papers: I. Britta M.
Institution: Karolinska Institutet.
μαγιο 2015 ολοσωμα ερκα INART -ΤΣΑΝΤΑ ΨΑΘΙΝΗ ΠΟΛΥΧΡΩΜΗ 42X16X32/55
Supervisor: Laurencikiene, Jurga. Publication year: Statistics Total Visits Views Novel Search DSpace. This Collection. United States. South Korea. United Kingdom.
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