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Molecules Important (molecule + important)
Selected AbstractsIncomplete effector/memory differentiation of antigen-primed CD8+ T,cells in gene gun DNA-vaccinated miceEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 7 2003Christina Bartholdy Abstract DNA vaccination is an efficient way to induce CD8+ T,cell memory, but it is still unclear to what extent such memory responses afford protection in vivo. To study this, we induced CD8+ memory responses directed towards defined viral epitopes, using DNA vaccines encoding immunodominant MHC class,I-restricted epitopes of lymphocytic choriomeningitis virus covalently linked to ,2-microglobulin. This vaccine construct primed for a stronger recall response than did a more conventional minigene construct. Despite this, vaccinated mice were only protected against systemic infection whereas protection against the consequences of peripheral challenge was limited. Phenotypic analysis revealed that DNA vaccine-primed CD8+ T,cells in uninfected mice differed from virus-primed CD8+ T,cells particularly regarding expression of very-late antigen (VLA)-4, an adhesion molecule important for targeting T,cells to inflammatory sites. Thus, our DNA vaccine induces a long-lived memory CD8+ T,cell population that provides efficient protection against high-dose systemic infection. However, viral replication in solid non-lymphoid organs is not curtailed sufficiently fast to prevent significant virus-induced inflammation. Our results suggest that this is due to qualitative limitations of the primed CD8+ T,cells. [source] Transcriptional changes in insulin- and lipid metabolism-related genes in the hippocampus of olfactory bulbectomized miceJOURNAL OF NEUROSCIENCE RESEARCH, Issue 14 2008Peter Gass Abstract Affymetrix chips were used to perform a hypothesis-free large-scale screening of transcripts in the hippocampus of olfactory bulbectomized mice, an established animal model of depression. Because only 11 transcripts were significantly changed, the statistically subsequent 25 transcripts below the significance level were additionally included in a first round of qRT-PCR evaluations. Furthermore, all 36 genes were then tested for mutual interactions or interactions with other molecules in a physiological context using PathwayArchitect software. Thirty of them were displayed in a network interacting with at least one partner molecule from the list or with other partner molecules known from the literature. All partner molecules from the most prominent 10 molecules of this network were then identified and put together into a new list. On those grounds, the hypothesis was made that metabolic network components of the insulin signaling pathway are perturbed in the disease. This pathway was subsequently tested by a second round of qRT-PCR, adding also a few additional candidate molecules belonging to this pathway. It turned out that the key target,FABP7,fell into the group of transcripts not significantly regulated within the chip data, and another key target,IRS1,did not show up in the chip experiments at all. In conclusion, our data reveal a problem with adhering to statistical significances in microarray experiments, insofar as molecules important for the disease may fall into the range of statistical noise. This approach may also be useful to find new targets for pharmacotherapy in affective disorders. © 2008 Wiley-Liss, Inc. [source] Ultraviolet radiation stimulates expression of Snail family transcription factors in keratinocytesMOLECULAR CARCINOGENESIS, Issue 4 2007Laurie G. Hudson Abstract The related zinc finger transcription factors Slug and Snail modulate epithelial mesenchymal transformation (EMT), the conversion of sessile epithelial cells into migratory fibroblast-like cells. EMT occurs during development, wound healing, and tumor progression. Growth factors, acting through mitogen-activated protein kinase (MAPK) cascades, regulate expression of Slug and Snail. Expression of Snail family transcription factors appears to be elevated in UVR-induced murine squamous cell carcinomas (SCC). We report here that ultraviolet radiation (UVR), which activates MAPK cascades, also stimulates Snail and Slug expression in epidermal keratinocytes. UVR exposure transiently elevated Slug and Snail mRNA expression in human keratinocytes in vitro and mouse epidermis in vivo. This induction was mediated, at least in part, through the ERK and p38 MAPK cascades, as pharmacological inhibition of these cascades partially or completely blocked Slug and Snail induction by UVR. On the other hand, UVR induction of Slug and Snail was enhanced by inhibition of JNK. Slug appears to play a functional role in the acute response of keratinocytes to UVR, as UVR induction of keratin 6 in the epidermis of Slug knockout mice was markedly delayed compared to wild-type mice. Slug and Snail are known to regulate molecules important in the cytoskeleton, intercellular adhesion, cell motility, and apoptosis, thus it seems probable that transiently or persistently elevated expression of these factors fosters the progression of UVR-induced SCC. © 2007 Wiley-Liss, Inc. [source] Quantitative proteome analysis of detergent-resistant membranes identifies the differential regulation of protein kinase C isoforms in apoptotic T cellsPROTEINS: STRUCTURE, FUNCTION AND BIOINFORMATICS, Issue 15 2010Therese Solstad Abstract Several lines of evidence suggest that detergent-resistant membranes (DRMs) (also known as lipid rafts and glycosphingolipid-enriched microdomains) may have a role in signaling pathways of apoptosis. Here, we developed a method that combines DRMs isolation and methanol/chloroform extraction with stable isotope labeling with amino acids in cell culture-based quantitative proteome analysis of DRMs from control and cisplatin-induced apoptotic Jurkat T cells. This approach enabled us to enrich proteins with a pivotal role in cell signaling of which several were found with increased or decreased amounts in DRMs upon induction of apoptosis. Specifically, we show that three isoforms of protein kinase C (PKC) are regulated differently upon apoptosis. Although PKC, which belongs to the group of conventional PKCs is highly up-regulated in DRMs, the levels of two novel PKCs, PKC, and PKC,, are significantly reduced. These alterations/differences in PKC regulation are verified by immunoblotting and confocal microscopy. In addition, a specific enrichment of PKC, in apoptotic blebs and buds is shown. Furthermore, we observe an increased expression of ecto-PKC, as a result of exposure to cisplatin using flow cytometry. Our results demonstrate that in-depth proteomic analysis of DRMs provides a tool to study differential localization and regulation of signaling molecules important in health and disease. [source] REVIEW ARTICLE: Uterine NK Cells, Spiral Artery Modification and the Regulation of Blood Pressure During Mouse PregnancyAMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 6 2010Suzanne D. Burke Citation Burke SD, Barrette VF, Gravel J, Carter ALI, Hatta K, Zhang J, Chen Z, Leno-Durán E, Bianco J, Leonard S, Murrant C, Adams MA, Anne Croy B. Uterine NK cells, spiral artery modification and the regulation of blood pressure during mouse pregnancy. Am J Reprod Immunol 2010 Reproductive success in mammals involves coordinated changes in the immune and cardiovascular as well as in the neuroendocrine and reproductive systems. This review addresses studies that identify potential links for NK cells and T cells with the local and systemic cardiovascular adaptations of pregnancy. The studies reviewed have utilized immunohistochemisty and in vivo analyses of vascular parameters by ultrasound, chronic monitoring of hemodynamics via radiotelemetric recording and intravital microscopy. At the uterine level, functional subsets of uterine natural killer cells were identified. These included subsets expressing molecules important for vasoregulation, in addition to those previously identified for angiogenesis. Spiral arteries showed conducted responses that could account for conceptus control of vasoactivity and mouse gestational blood pressure 5-phase pattern. Vascular immunology is an emerging transdisciplinary field, critical for both reproductive immunology and cardiovascular disease. [source] Principles of immunosuppression in uveitisACTA OPHTHALMOLOGICA, Issue 2009F WILLERMAIN Non infectious uveitis is a heterogeneous group of diseases mediated through autoimmune and autoinflammatory mechanisms. It is thus crucial to perform a complete work-up to characterise the disease and eventually find a precise aetiology or a systemic associated condition. When the inflammation is bilateral and the vision threatened, systemic drugs are usually proposed. Despite tremendous progress in the understanding of the disease, treatments are generally based on the administration of non specific immunosuppressive molecules. Currently, high doses oral corticosteroids are first given, followed by a slow tapering of the dosage. If this strategy does not lead to disease control, a steroid-sparing agent should be considered. Antimetabolites, T-cell inhibitor and alkylating agents will be chosen (alone or in combination), depending on the severity of the disease and patients general status. Recently the development of biologic agents offers the possibility to target various specific molecules important in non infectious uveitis development. Nowadays, anti-TNF, have been mostly tested with encouraging results. However, it is likely that different uveitis subtypes would require different biologic agents. In the future, the growing production of specific inhibitors might lead to a more tailored approach of uveitis treatment. [source] | ||||||||||