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Important Transcription Factors (important + transcription_factor)
Selected AbstractsRole of protease-activated receptor-2 during cutaneous inflam-mation and the immune responseEXPERIMENTAL DERMATOLOGY, Issue 9 2004M. Steinhoff Protease-activated receptors (PARs) constitute a new subfamily of G-protein-coupled receptors with seven transmembrane domains which are activated by various serine proteases such as thrombin, cathepsin G, trypsin or tryptase, and bacterial proteases or mite antigens, for example. PAR2 is a receptor for mast cell tryptase or house dust mite allergens, which is released during inflammation and allergic reactions. In the skin, PAR2 is diversely expressed by keratinocytes, endothelial cells, and occasionally sensory nerves of human skin in various disease states. Moreover, immunocompetent cells such as T cells and neutrophils express functional PAR2, thereby contributing to inflammation and host defense. Own data revealed that PAR2 contributes to neurogenic inflammation by releasing neuropeptides from sensory nerves resulting in oedema, plasma extravasation and infiltration of neutrophils. Thus, mast cells may communicate with sensory nerves in inflammatory tissues by activating PAR2 via tryptase. Moreover, PAR2 agonists upregulate the expression of certain cell-adhesion molecules and cytokines such as interleukin-6 and interleukin-8 on dermal microvascular endothelial cells or regulate neutrophil migration, indicating that PAR2 plays an important role in leucocyte/endothelial interactions. These effects may be partly mediated by NF-,B, an important transcription factor during inflammation and immune response. PAR2 stimulation results in the activation of NF-,B on microvascular endothelial cells and keratinocytes, thereby regulating ICAM-1 expression. We also demonstrate evidence for a diverse expression of PAR2 in various skin diseases and highlight the recent knowledge about the important role of PAR2 during inflammation and the immune response. Together, PAR2 -modulating agents may be new tools for the treatment of inflammatory and allergic diseases in the skin. [source] Magnetic resonance imaging and biological properties of pancreatic islets labeled with iron oxide nanoparticlesNMR IN BIOMEDICINE, Issue 8 2009Hoe Suk Kim Abstract This study was undertaken to investigate the in vitro effect of islet labeling with iron oxide nanoparticles for MRI on islet viability, insulin secretion, and gene expression. Isolated rat islets were labeled with Resovist (25,200,µg Fe/mL, a clinically approved MRI contrast agent) in the presence or absence of poly- l -Lysine (PLL, 1.5,µg/mL) for 48,h. The iron content of labeled islets was found to increase in a dose-dependent manner. More than 90% of the islets were labeled with 100,µg Fe/mL. We confirmed the localizations of iron oxide nanoparticles within islet , -cells by insulin immunostaining. As the concentration of Resovist increased, T2 values as determined by T2 -weighted MRI on a 1.5,Tesla MR scanner decreased. Labeling of 100 islets in a medium containing 100,µg Fe/mL of Resovist in the absence of PLL provided sufficient contrast for islet visualization on T2 -weighted MRI. MTT assays showed that the viability of labeled islets was not different from that of unlabeled islets. No statistical difference was observed between labeled (2.91,±,0.36) and unlabeled islets (2.83,±,0.61) in terms of the ability to secrete insulin, as determined by the glucose stimulation index. We also evaluated the effect of iron oxide incorporation on the gene expressions in islet cells using RT-PCR (reverse transcriptase PCR). Insulin expression in labeled islets was significantly elevated (1.83,±,0.25 fold vs. unlabeled; p,=,0.005), but not the expression of somatostatin (1.39,±,0.18 fold vs. unlabeled; p,=,0.085) or glucagons (1.28,±,0.13 fold vs. unlabeled; p,=,0.09). Expression of an important transcription factor for insulin gene transcription, BETA2 (beta-cell E-box trans-activator), was increased in labeled islets (1.67,±,0.15 fold vs. unlabeled; p,=,0.029). The findings of this study indicate that Resovist provides a satisfactory means to image islets and has no deleterious effect on islet function or gene expression. Copyright © 2009 John Wiley & Sons, Ltd. [source] Arabidopsis WRKY33 transcription factor is required for resistance to necrotrophic fungal pathogensTHE PLANT JOURNAL, Issue 4 2006Zuyu Zheng Summary Plant WRKY transcription factors are key regulatory components of plant responses to microbial infection. In addition to regulating the expression of defense-related genes, WRKY transcription factors have also been shown to regulate cross-talk between jasmonate- and salicylate-regulated disease response pathways. The two pathways mediate resistance against different types of microbial pathogens, and there are numerous reports of antagonistic interactions between them. Here we show that mutations of the Arabidopsis WRKY33 gene encoding a WRKY transcription factor cause enhanced susceptibility to the necrotrophic fungal pathogens Botrytis cinerea and Alternaria brassicicola concomitant with reduced expression of the jasmonate-regulated plant defensin PDF1.2 gene. Ectopic over-expression of WRKY33, on the other hand, increases resistance to the two necrotrophic fungal pathogens. The wrky33 mutants do not show altered responses to a virulent strain of the bacterial pathogen Pseudomonas syringae, although the ectopic expression of WRKY33 results in enhanced susceptibility to this pathogen. The susceptibility of WRKY33 -over-expressing plants to P. syringae is associated with reduced expression of the salicylate-regulated PR-1 gene. The WRKY33 transcript is induced in response to pathogen infection, or treatment with salicylate or the paraquat herbicide that generates activated oxygen species in exposed cells. WRKY33 is localized to the nucleus of plant cells and recognizes DNA molecules containing the TTGACC W-box sequence. Together, these results indicate that pathogen-induced WRKY33 is an important transcription factor that regulates the antagonistic relationship between defense pathways mediating responses to P. syringae and necrotrophic pathogens. [source] RNT-1 regulation in C. elegansJOURNAL OF CELLULAR BIOCHEMISTRY, Issue 1 2005Yon Ju Ji Abstract RUNXs are important transcription factors, which are involved in animal development and human carcinogenesis. RNT-1, the only homologue of RUNXs, in Caenorhabditis elegans (C. elegans) has been identified and viable mutant animals of rnt-1 gene have been isolated and characterized recently. Genetic analyses using rnt- 1 mutants have shown that RNT-1 is regulated by TGF,- and Wnt-signaling pathways in the body size regulation and male tail development. Here, we review our current understanding of RNT-1 functions in these signaling pathways. Furthermore, future prospects of RNT-1 and BRO-1 studies in C. elegans are discussed in this review. © 2005 Wiley-Liss, Inc. [source] Aging and disease: connections to sirtuinsAGING CELL, Issue 2 2010Gizem Donmez Summary The sirtuins are highly conserved NAD-dependent deacetylases that were shown to regulate lifespan in lower organisms and affect diseases of aging in mammals, such as diabetes, cancer, and inflammation. Most relevant to the amelioration of disease, the SIR2 ortholog SIRT1 has been shown to deacetylate many important transcription factors to exert an overarching influence on numerous metabolic pathways. Here we discuss several diseases of aging for which SIRT1 has been recently shown to confer protection. These findings suggest that manipulating sirtuin activity pharmacologically may be a fruitful area to improve human health. [source] Effect of vertebroplasty filler materials on viability and gene expression of human nucleus pulposus cellsJOURNAL OF ORTHOPAEDIC RESEARCH, Issue 5 2008Áron Lazáry Abstract Consequences of intradiscal cement leakage,often occurring after vertebral cement augmentation for the treatment of vertebral compression fractures,are still unknown. In this study, we have investigated the influences of vertebroplasty filler materials (polymethylmethacrylate-, calcium phosphate- and calcium sulfate-based bone cement) on isolated nucleus pulposus cells. Cell viability of cultured human nucleus pulposus cells were measured after treatment with vertebroplasty filler materials. Gene expression profile of selected genes was determined with quantitative real-time PCR. The widely used polymethylmethacrylate and calcium phosphate cement significantly decreased cell number in a dose- and time-dependent manner while calcium sulfate cement affected cell viability less. Expression of genes involved in matrix metabolism of nucleus pulposus,aggrecan, collagens, small proteoglycans,as well as important transcription factors have also significantly changed due to treatment (e.g., 2.5-fold decrease in aggrecan expression was determined in cultures due to polymethylmethacrylate treatment). Our results suggest that vertebroplasty filler materials,depending on the type of applied material,can accelerate the degeneration of nucleus pulposus cells resulting in a less flexible disc in case of intradiscal cement leakage. This process may increase the risk of a subsequent new vertebral fracture, the main complication of vertebral augmentation. © 2008 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 26:601,607, 2008 [source] Signal transduction of inflammatory cytokines and tumor developmentCANCER SCIENCE, Issue 6 2006Akihiko Yoshimura It has been estimated that >20% of all malignancies are initiated or exacerbated by inflammation. Until recently, the molecular basis of this process has not been clarified. However, recent studies have uncovered the molecular mechanism of intracellular signaling pathways of inflammatory cytokines such as tumor necrosis factor (TNF)-,, interferon (IFN)-, and interleukin (IL)-6. Three major transcription factors including NF-,B, STAT1 and STAT3 have been shown to play major roles in transmitting inflammatory cytokine signals to the nucleus. One function of NF-,B and STAT3 in tumor cells is the promotion of cell growth and cell survival through the induction of target genes, whose products promote cell division and inhibit apoptosis. In addition, NF-,B and STAT1 are important transcription factors that induce inflammatory mediators from inflammatory cells, especially macrophages, while STAT3 often antagonizes this process. STAT1 is generally believed to be an anti-oncogene because it promotes apoptosis through p53, but it could promote inflammation-mediated tumor development by enhancing tissue injury, remodeling, fibrosis and inflammation. Hence, the inhibition of NF-,B and STATs offers a strategy for treatment of a variety of malignancies and can convert inflammation-induced tumor growth into inflammation-induced tumor regression. (Cancer Sci 2006; 97) [source] | |||||||||||||