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Elevated Production (elevated + production)
Selected AbstractsGlucocorticoid-induced TNFR family-related protein (GITR) activation exacerbates murine asthma and collagen-induced arthritisEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 12 2005Manish Patel Abstract Glucocorticoid-induced TNFR family-related protein (GITR) is expressed at low levels on resting T cells, B cells and macrophages but at high levels on regulatory T cells (Treg). Although GITR expression is up-regulated on CD4+ effector cells upon activation, the role of GITR in Th1 and Th2 cell development is unclear. We report here that activation of GITR signalling by anti-GITR antibody markedly enhanced the induction of both Th1 and Th2 cytokine production by naive CD4+CD25, T cells. Consistent with this observation, anti-GITR antibody significantly enhanced the expression of the key Th1 (T-bet) and Th2 (GATA3) transcription factors in vitro. Administration of anti-GITR mAb in a murine model of arthritis significantly exacerbated the severity and onset of joint inflammation with elevated production of TNF-,, IFN-,, IL-5, and collagen-specific IgG1. Administration of anti-GITR mAb also significantly exacerbated murine allergic airways inflammation with elevated production of OVA-specific IFN-,, IL-2, IL-4, IL-5, and IgE. Finally, we demonstrated that adoptive transfer of CD4+GITR+ T cells effectively abolished airway inflammation induced in SCID mice reconstituted with CD4+GITR, T cells. Our results therefore provide direct evidence that GITR can modulate both Th1- and Th2-mediated inflammatory diseases, and may be a potential target for therapeutic intervention. [source] Quantitative analysis of the synthesis and secretion of type VII collagen in cultured human dermal fibroblasts with a sensitive sandwich enzyme-linked immunoassayEXPERIMENTAL DERMATOLOGY, Issue 2 2007Satoshi Amano Abstract:, Type VII collagen is the major component of anchoring fibrils in the epidermal basement membrane. Its expression has been analyzed by immunostaining or Northern blotting, but rarely at the protein level. In this study, we have quantitatively examined the effects of ascorbic acid and various cytokines/growth factors on the protein synthesis and secretion of type VII collagen by human dermal fibroblasts in culture, using a developed, highly sensitive sandwich enzyme-linked immunoassay with two kinds of specific monoclonal antibodies against the non-collagenous domain-1. Ascorbic acid and its derivative induced a twofold increase in type VII collagen synthesis, and markedly increased the secretion of type VII collagen into the medium when compared with the control culture. This effect was not influenced by the presence of transforming growth factor- ,1 (TGF- ,1). The synthesis of type VII collagen was elevated by TGF- ,1, platelet-derived growth factor, tumor necrosis factor- ,, and interleukin-1,, but not by TGF- ,. Thus, our data indicate that the synthesis and secretion of type VII collagen in human dermal fibroblasts are regulated by ascorbate and the enhancement of type VII collagen gene expression by cytokines/growth factors is accompanied with elevated production of type VII collagen at the protein level. [source] Fission yeast decaprenyl diphosphate synthase consists of Dps1 and the newly characterized Dlp1 protein in a novel heterotetrameric structureFEBS JOURNAL, Issue 20 2003Ryoichi Saiki The analysis of the structure and function of long chain-producing polyprenyl diphosphate synthase, which synthesizes the side chain of ubiquinone, has largely focused on the prokaryotic enzymes, and little is known about the eukaryotic counterparts. Here we show that decaprenyl diphosphate synthase from Schizosaccharomyces pombe is comprised of a novel protein named Dlp1 acting in partnership with Dps1. Dps1 is highly homologous to other prenyl diphosphate synthases but Dlp1 shares only weak homology with Dps1. We showed that the two proteins must be present simultaneously in Escherichia coli transformants before ubiquinone-10, which is produced by S. pombe but not by E. coli, is generated. Furthermore, the two proteins were shown to form a heterotetrameric complex. This is unlike the prokaryotic counterparts, which are homodimers. The deletion mutant of dlp1 lacked the enzymatic activity of decaprenyl diphosphate synthase, did not produce ubiquinone-10 and had the typical ubiquinone-deficient S. pombe phenotypes, namely hypersensitivity to hydrogen peroxide, the need for antioxidants for growth on minimal medium and an elevated production of H2S. Both the dps1 (formerly dps) and dlp1 mutants could generate ubiquinone when they were transformed with a bacterial decaprenyl diphosphate synthase, which functions in its host as a homodimer. This indicates that both dps1 and dlp1 are required for the S. pombe enzymatic activity. Thus, decaprenyl diphosphate from a eukaryotic origin has a heterotetrameric structure that is not found in prokaryotes. [source] Expression of Fibroblast Growth Factor-2 in the Nucleus Ambiguus Following Recurrent Laryngeal Nerve Injury in the RatTHE LARYNGOSCOPE, Issue 12 2000Tetsuji Sanuki MD Abstract Objectives To examine fibroblast growth factor-2 (FGF-2) immunoreactivity in the nucleus ambiguus (NA) after three different recurrent laryngeal nerve (RLN) injuries. Study Design Immunohistochemical analysis of FGF-2. Methods Thirty adult rats underwent left-sided RLN crush (group A). The left RLN was transected in groups B (n = 30) and C (n = 30); in group C, both nerve stumps were covered with silicone caps. FGF-2 in the NA was assessed as the ratio of the positive areas on the left (operated [O]) and right (unoperated [U]) sides. The ratio (O/U) was measured 1, 3, 7, 14, and 28 days after the procedure. Three rats underwent left-sided RLN exposure and were killed 7 days later (control). Results Left-sided RLN paralysis occurred until day 28 in group A. In the control group, O/U was approximately 1. In group A, O/U was significantly elevated on day 7; in group B, on days 3, 7, and 14; and in group C, on day 3. O/U in group B was significantly greater than that in group A on days 14 and 28. Maximal FGF-2 immunoreactivity was significantly lower in group C than in groups A and B. Conclusions We demonstrated elevated production of FGF-2 in the NA after RLN injury. This endogenous FGF-2 might contribute to preventing lesion-induced neuronal death. Blockage of axonal regeneration might suppress FGF-2 production in the NA. Further understanding of the roles of FGF-2 after RLN in-jury may contribute to the prevention of neuronal death and facilitation of axonal regeneration. [source] Mutation screening of interferon regulatory factor 1 gene (IRF-1) as a candidate gene for atopy/asthmaCLINICAL & EXPERIMENTAL ALLERGY, Issue 11 2000E. Noguchi Background IL-4 gene cluster on chromosome 5 contains several candidate genes for atopy and asthma. Several independent studies have shown evidence for linkage between the markers flanking IL-4 gene cluster and asthma and/or asthma-related traits. Interferon regulatory factor 1 (IRF-1) is located approximately 300 kb telomeric to IL-4 and recent study reveals that IRF-1 deficiency results in an elevated production of Th2-related cytokines and a compensatory decrease in the expression of native cell- and Th1-related cytokines. Objective To determine if there are any mutations associated with the development of atopy and asthma present in the coding exons and 5, flanking region of the IRF-1 gene. Methods and results We have screened the promoter and coding regions of the IRF-1 gene in atopic asthmatics and controls by SSCP method. We found three novel nuclear variants (the ,300G/T and 4396 A/G polymorphisms and the 6355G > A rare variant) in the IRF-1 gene. No variants causing amino acid alterations of IRF-1 were detected. The ,300G/T polymorphism was in nearly complete linkage disequilibrium with the 4396 A/G polymorphism. An association between the 4396 A > G polymorphism and atopy/asthma was examined by transmission disequilibrium test in 81 asthmatic families. Either of 4396 A or 4396G alleles was not significantly preferentially transmitted to atopy- or asthma-affected children. Conclusion The IRF-1 gene is less likely to play a substantial role in the development of atopy and asthma in the Japanese population. [source] | ||||||||||