Search results for "Dual Specificity Phosphatase 1"
showing 6 items of 6 documents
The RNA binding protein tristetraprolin influences the activation state of murine dendritic cells
2010
Abstract Dendritic cells (DCs) serve to maintain peripheral tolerance under steady state conditions. Upon triggering by activation signals they initiate strong immune responses. The activation of DCs is accompanied by a rapid upregulation of proinflammatory cytokines, which were shown in other cell types to be regulated by mechanisms at the transcriptional and posttranscriptional level. Tristetraprolin (TTP), an important RNA binding protein, is involved in the regulation of mRNA stability of such cytokines. In this study we analyzed the significance of TTP for mouse DCs, which were derived from TTP −/− and WT bone marrow progenitor cells (BM-DCs). Unstimulated BM-DCs of TTP −/− mice expres…
Evaluation of the Role of Candida albicans Agglutinin-Like Sequence (Als) Proteins in Human Oral Epithelial Cell Interactions
2012
The fungus C. albicans uses adhesins to interact with human epithelial surfaces in the processes of colonization and pathogenesis. The C. albicans ALS (agglutinin-like sequence) gene family encodes eight large cell-surface glycoproteins (Als1-Als7 and Als9) that have adhesive function. This study utilized C. albicans Δals mutant strains to investigate the role of the Als family in oral epithelial cell adhesion and damage, cytokine induction and activation of a MAPK-based (MKP1/c-Fos) signaling pathway that discriminates between yeast and hyphae. Of the eight Δals mutants tested, only the Δals3 strain showed significant reductions in oral epithelial cell adhesion and damage, and cytokine pro…
Aplidin® induces JNK-dependent apoptosis in human breast cancer cells via alteration of glutathione homeostasis, Rac1 GTPase activation, and MKP-1 ph…
2006
Aplidin® is an antitumor agent in phase II clinical trials that induces apoptosis through the sustained activation of Jun N-terminal kinase (JNK). We report that Aplidin® alters glutathione homeostasis increasing the ratio of oxidized to reduced forms (GSSG/GSH). Aplidin® generates reactive oxygen species and disrupts the mitochondrial membrane potential. Exogenous GSH inhibits these effects and also JNK activation and cell death. We found two mechanisms by which Aplidin® activates JNK: rapid activation of Rac1 small GTPase and downregulation of MKP-1 phosphatase. Rac1 activation was diminished by GSH and enhanced by L-buthionine (SR)-sulfoximine, which inhibits GSH synthesis. Downregulatio…
Dual specificity phosphatase 1 knockout mice show enhanced susceptibility to anaphylaxis but are sensitive to glucocorticoids.
2007
Dual specificity phosphatase DUSP1 (otherwise known as mitogen-activated phosphatase 1 or MKP-1) dephosphorylates MAPKs, particularly p38, and negatively regulates innate immunity. Recent studies have shown that the DUSP1 gene is transcriptionally up-regulated by glucocorticoids (GCs) and that the antiinflammatory action of GCs is impaired in DUSP1-/- mice. Here we show that GC-mediated dephosphorylation of ERK-1 and ERK-2 activated by IgE receptor cross-linking is unimpaired in bone marrow-derived mast cells (BMMCs) of DUSP1-/- mice. Dephosphorylation of phospho-p38 MAPK is impaired but only at early times of GC treatment. Proinflammatory cytokine and chemokine gene expression (CCL2, IL-6,…
SARS CoV2 infection _The longevity study perspectives
2021
Graphical abstract
Glucocorticoids inhibit MAP kinase via increased expression and decreased degradation of MKP-1
2001
Glucocorticoids inhibit the proinflammatory activities of transcription factors such as AP-1 and NF-kappa B as well as that of diverse cellular signaling molecules. One of these signaling molecules is the extracellular signal-regulated kinase (Erk-1/2) that controls the release of allergic mediators and the induction of proinflammatory cytokine gene expression in mast cells. The mechanism of inhibition of Erk-1/2 activity by glucocorticoids is unknown. Here we report a novel dual action of glucocorticoids for this inhibition. Glucocorticoids increase the expression of the MAP kinase phosphatase-1 (MKP-1) gene at the promoter level, and attenuate proteasomal degradation of MKP-1, which we re…