9
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: not found

      Expression of the NF-κB inhibitor ABIN-3 in response to TNF and toll-like receptor 4 stimulation is itself regulated by NF-κB

      research-article

      Read this article at

      ScienceOpenPublisherPMC
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Although the nuclear factor-κB (NF-κB)-dependent gene expression is critical to the induction of an efficient immune response to infection or tissue injury, excessive or prolonged NF-κB signalling can contribute to the development of several inflammatory diseases. Therefore, the NF-κB signal transduction pathway is tightly regulated by several intracellular proteins. We have previously identified A20-binding inhibitor of NF-κB activation (ABIN)-3 as an lipopolysaccharide (LPS)-inducible protein in monocytes that negatively regulates NF-B activation in response to tumour necrosis factor (TNF) and LPS. Here we report that ABIN-3 expression is also up-regulated upon TNF treatment of monocytes and other non-myeloid cell types. We also found a significantly enhanced expression of ABIN-3 in monocytes of sepsis patients, which is restored to control levels by corticotherapy. To further understand the transcriptional regulation of ABIN-3 expression, we isolated the human ABIN-3 promoter and investigated its activation in response to TNF and LPS. This revealed that the LPS- and TNF-inducible expression of ABIN-3 is dependent on the binding of NF-κB to a specific B site in the ABIN-3 promoter. Altogether, these data indicate an important role for NF-κB-dependent gene expression of ABIN-3 in the negative feedback regulation of TNF receptor and toll-like receptor 4 induced NF-κB activation.

          Related collections

          Most cited references18

          • Record: found
          • Abstract: found
          • Article: not found

          A new Simplified Acute Physiology Score (SAPS II) based on a European/North American multicenter study.

          To develop and validate a new Simplified Acute Physiology Score, the SAPS II, from a large sample of surgical and medical patients, and to provide a method to convert the score to a probability of hospital mortality. The SAPS II and the probability of hospital mortality were developed and validated using data from consecutive admissions to 137 adult medical and/or surgical intensive care units in 12 countries. The 13,152 patients were randomly divided into developmental (65%) and validation (35%) samples. Patients younger than 18 years, burn patients, coronary care patients, and cardiac surgery patients were excluded. Vital status at hospital discharge. The SAPS II includes only 17 variables: 12 physiology variables, age, type of admission (scheduled surgical, unscheduled surgical, or medical), and three underlying disease variables (acquired immunodeficiency syndrome, metastatic cancer, and hematologic malignancy). Goodness-of-fit tests indicated that the model performed well in the developmental sample and validated well in an independent sample of patients (P = .883 and P = .104 in the developmental and validation samples, respectively). The area under the receiver operating characteristic curve was 0.88 in the developmental sample and 0.86 in the validation sample. The SAPS II, based on a large international sample of patients, provides an estimate of the risk of death without having to specify a primary diagnosis. This is a starting point for future evaluation of the efficiency of intensive care units.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Signal-induced site-specific phosphorylation targets I kappa B alpha to the ubiquitin-proteasome pathway.

            The transcription factor NF-kappa B is sequestered in the cytoplasm by the inhibitor protein I kappa B alpha. Extracellular inducers of NF-kappa B activate signal transduction pathways that result in the phosphorylation and subsequent degradation of I kappa B alpha. At present, the link between phosphorylation of I kappa B alpha and its degradation is not understood. In this report we provide evidence that phosphorylation of serine residues 32 and 36 of I kappa B alpha targets the protein to the ubiquitin-proteasome pathway. I kappa B alpha is ubiquitinated in vivo and in vitro following phosphorylation, and mutations that abolish phosphorylation and degradation of I kappa B alpha in vivo prevent ubiquitination in vitro. Ubiquitinated I kappa B alpha remains associated with NF-kappa B, and the bound I kappa B alpha is degraded by the 26S proteasome. Thus, ubiquitination provides a mechanistic link between phosphorylation and degradation of I kappa B alpha.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              The interplay between the glucocorticoid receptor and nuclear factor-kappaB or activator protein-1: molecular mechanisms for gene repression.

              The inflammatory response is a highly regulated physiological process that is critically important for homeostasis. A precise physiological control of inflammation allows a timely reaction to invading pathogens or to other insults without causing overreaction liable to damage the host. The cellular signaling pathways identified as important regulators of inflammation are the signal transduction cascades mediated by the nuclear factor-kappaB and the activator protein-1, which can both be modulated by glucocorticoids. Their use in the clinic includes treatment of rheumatoid arthritis, asthma, allograft rejection, and allergic skin diseases. Although glucocorticoids have been widely used since the late 1940s, the molecular mechanisms responsible for their antiinflammatory activity are still under investigation. The various molecular pathways proposed so far are discussed in more detail.
                Bookmark

                Author and article information

                Journal
                J Cell Mol Med
                J. Cell. Mol. Med
                jcmm
                Journal of Cellular and Molecular Medicine
                Blackwell Publishing Ltd (Oxford, UK )
                1582-1838
                1582-4934
                January 2008
                10 December 2007
                : 12
                : 1
                : 316-329
                Affiliations
                [a ]Unit of Molecular Signal Transduction in Inflammation, Department for Molecular Biomedical Research, Ghent, Belgium
                [b ]Department for Molecular Biology, Ghent University, Technologiepark, Ghent, Belgium
                [c ]Cytokines and Inflammation Unit, Institut Pasteur, Paris, France
                [d ]Service de Réanimation, Hopital Delafontaine, Saint-Denis, France
                Author notes
                Correspondence to: Prof. Dr. Rudi BEYAERT, Ghent University-VIB, Dept.for Molecular Biomedical Research, Technologiepark 927, B-9052 Ghent, Belgium. Tel.: +32 93 31 37 70 Fax: +32 93 31 36 09 E-mail: rudi.beyaert@ 123456dmbr.ugent.be
                Article
                10.1111/j.1582-4934.2007.00187.x
                3823492
                18081698
                6aeb6463-13b7-469a-8317-19324a059365
                2008 The Authors Journal compilation © 2008 Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd
                History
                : 01 October 2007
                : 23 November 2007
                Categories
                In Focus

                Molecular medicine
                nf-κb,signal transduction,sepsis,lipopolysaccharide,tnf,toll-like receptors
                Molecular medicine
                nf-κb, signal transduction, sepsis, lipopolysaccharide, tnf, toll-like receptors

                Comments

                Comment on this article