Search results for "Up-Regulation"

DNA damage causes TP53-dependent coupling of self-renewal and senescence pathways in embryonal carcinoma cells.

2013

Recent studies have highlighted an apparently paradoxical link between self-renewal and senescence triggered by DNA damage in certain cell types. In addition, the finding that TP53 can suppress senescence has caused a re-evaluation of its functional role in regulating these outcomes. To investigate these phenomena and their relationship to pluripotency and senescence, we examined the response of the TP53-competent embryonal carcinoma (EC) cell line PA-1 to etoposide-induced DNA damage. Nuclear POU5F1/OCT4A and P21CIP1 were upregulated in the same cells following etoposide-induced G 2M arrest. However, while accumulating in the karyosol, the amount of OCT4A was reduced in the chromatin fract…

Age-related changes in the regulation of transcription factor NF-kappa B in rat brain.

1997

Aging process involves an increase in stress at cellular level. We studied whether aging affects the regulation of stress responsive transcription factor NF-kappa B in brain samples of Wistar rats. Hippocampus, cerebellum, and temporal and frontal lobes of cortex were studied. We observed a significant up-regulation in the constitutive, nucleus-located NF-kappa B binding activity in 30-month-old Wistar rats compared to young and 18-month-old rats. The increase was most prominent in cerebellum and in frontal cortex, but age-related changes did not occur in hippocampus. Inducible, cytoplasmic NF-kappa B binding activity was not affected by aging in any of the samples studied. Western blot ass…

Modulation of MMP-2 and MMP-9 in Churg-Strauss syndrome respiratory mucosa: potential monitoring parameters.

2014

Churg-Strauss (CSS) syndrome is rare and of unknown etiology. It is associated with vasculitis, blood eosinophilia and granulomatosis, and affects multiple organs and systems at various stages of the disease. Specific diagnostic and monitoring tests are not yet available. This study aims to assess the changes in MMP-2 and MMP-9 along with the histopathological alterations in two cases of CSS, as possible potential diagnostic and monitoring criteria. Two adult male patients were diagnosed with CSS in the otorhinolaryngology clinic in the University of Palermo, based on multiple clinical and histopathologic criteria. Biopsies of respiratory mucosa were taken after the consent of the patients…

R-Rescovitine (Seliciclib) inhibits DNA damage-induced Cyclin A1 up-regulation and hinders non-homologous end joining: a rationale for therapeutic co…

2011

Dacarbazine-mediated upregulation of NKG2D ligands on tumor cells activates NK and CD8 T cells and restrains melanoma growth.

2013

International audience; Dacarbazine (DTIC) is a cytotoxic drug widely used for melanoma treatment. However, the putative contribution of anticancer immune responses in the efficacy of DTIC has not been evaluated. By testing how DTIC affects host immune responses to cancer in a mouse model of melanoma, we unexpectedly found that both natural killer (NK) and CD8(+) T cells were indispensable for DTIC therapeutic effect. Although DTIC did not directly affect immune cells, it triggered the upregulation of NKG2D ligands on tumor cells, leading to NK cell activation and IFNγ secretion in mice and humans. NK cell-derived IFNγ subsequently favored upregulation of major histocompatibility complex cl…

SNAT2 silencing prevents the osmotic induction of transport system A and hinders cell recovery from hypertonic stress.

2005

AbstractUnder hypertonic conditions the induction of SLC38A2/SNAT2 leads to the stimulation of transport system A and to the increase in the cell content of amino acids. In hypertonically stressed human fibroblasts transfection with two siRNAs for SNAT2 suppressed the increase in SNAT2 mRNA and the stimulation of system A transport activity. Under the same condition, the expansion of the intracellular amino acid pool was significantly lowered and cell volume recovery markedly delayed. It is concluded that the up-regulation of SNAT2 is essential for the rapid restoration of cell volume after hypertonic stress.

Selenium affects biosilica formation in the demosponge Suberites domuncula

2005

Selenium is a trace element found in freshwater and the marine environment. We show that it plays a major role in spicule formation in the demosponge Suberites domuncula. If added to primmorphs, an in vitro sponge cell culture system, it stimulates the formation of siliceous spicules. Using differential display of transcripts, we demonstrate that, after a 72-h exposure of primmorphs to selenium, two genes are up-regulated; one codes for selenoprotein M and the other for a novel spicule-associated protein. The deduced protein sequence of selenoprotein M (14 kDa) shows characteristic features of metazoan selenoproteins. The spicule-associated protein (26 kDa) comprises six characteristic repe…

Subcellular localization and characterization of nitric oxide synthase(s) in endothelial cells: physiological implications.

1994

Endothelial cells (EC) contain a constitutive Ca2+/calmodulin-dependent nitric oxide (NO) synthase (cNOS) which plays an important role in the local control of vascular tone. We compared the subcellular distribution of this enzyme in cultured and freshly isolated pig EC by determination of specific cNOS activity and immunoblot analysis. Similar studies were also performed with cultured and freshly isolated bovine and cultured human EC. Enzyme activity was predominantly (> 70%) associated with the particulate fraction of all EC types tested and was highest in freshly isolated porcine EC. Both specific cNOS activity and immunoreactivity were substantially higher (> 3-fold) in th…

T helper cell polarisation in coeliac disease: any (T-)bet ?

2004

Recent data strongly support the view that coeliac disease is a Th1 mediated inflammatory disease as both interferon γ production and T-bet levels in gut infiltrating cells are upregulated The puzzling observation on high interferon γ (IFN-γ) but low interleukin (IL)-12 levels in coeliac disease (CD) has resulted in questions about the underlying principles of T helper cell polarisation. In this issue of G ut ,1 the molecular basis of T helper cell polarisation in CD has been illuminated by the finding that T-bet, the master transcription factor of T helper cell type 1 (Th1) cells, is upregulated in this disease [see page 1090] . The past decade has witnessed a dramatic improvement in our p…

Cutting Edge: A Key Pathogenic Role of IL-27 in T Cell- Mediated Hepatitis

2007

Abstract The signals driving T cell activation in T cell-mediated fulminant hepatitis are not fully understood. In this study, we identify the cytokine IL-27p28/EBI3 as a major pathogenic factor in the ConA model of T cell-mediated hepatitis. We found an up-regulation of hepatic EBI3 and p28 expression and augmented levels of IL-27 in wild-type mice after ConA administration, suggesting a potential pathogenic role of this cytokine in ConA hepatitis. Consistently, IL-27 EBI3-deficient mice were almost completely protected from ConA-induced liver damage. Such protection was associated with reduced levels of IFN-γ and its signaling proteins pSTAT-1 and T-bet. Finally, in vivo blockade of IL-27…