Endotoxic shock in AUF1 knockout mice mediated by failure to degrade proinflammatory cytokine mRNAs.

Endotoxic shock in AUF1 knockout mice mediated by failure to degrade proinflammatory cytokine mRNAs. Research Abstract Details 

Research Abstract Table of Contents

Jump to the:

Endotoxic shock in AUF1 knockout mice mediated by failure to degrade proinflammatory cytokine mRNAs. Abstract Text:

Jin-Yu Lu,Navid Sadri,Robert J Schneider,

Excessive production of proinflammatory cytokines, particularly tumor necrosis factor-alpha (TNFalpha) and interleukin-1beta (IL-1beta), plays a critical role in septic shock induced by bacterial endotoxin (endotoxemia). Precise control of cytokine expression depends on rapid degradation of cytokine mRNAs, mediated by an AU-rich element (ARE) in the 3' noncoding region and by interacting ARE-binding proteins, which control the systemic inflammatory response. To understand the function of the ARE-binding protein AUF1, we developed an AUF1 knockout mouse. We show that AUF1 normally functions to protect against the lethal progression of endotoxemia. Upon endotoxin challenge, AUF1 knockout mice display symptoms of severe endotoxic shock, including vascular hemorrhage, intravascular coagulation, and high mortality, resulting from overproduction of TNFalpha and IL-1beta. Overexpression of these two cytokines is specific, and shown to result from an inability to rapidly degrade these mRNAs in macrophages following induction. Neutralizing antibodies to TNFalpha and IL-1beta protect AUF1 knockout mice against lethal endotoxic shock. These and other data describe a novel post-transcriptional mechanism whereby AUF1 acts as a crucial attenuator of the inflammatory response, promoting the rapid decay of selective proinflammatory cytokine mRNAs following endotoxin activation. Defects in the AUF1 post-transcriptionally controlled pathway may be involved in human inflammatory disease.

Endotoxic shock in AUF1 knockout mice mediated by failure to degrade proinflammatory cytokine mRNAs. Publishing Authors By Initials

JY Lu,N Sadri,RJ Schneider,

For similar peptides: intercellular signaling peptides and proteins: cytokines: monokines: tumor necrosis factor-alpha research abstracts see: peptides: intercellular signaling peptides and proteins: cytokines: monokines: tumor necrosis factor-alpha research

PUBMED ID PMID:

MEDLINE DATE:

Endotoxic shock in AUF1 knockout mice mediated by failure to degrade proinflammatory cytokine mRNAs. Journal Published:

PUBLICATION TYPE: Research Support, N.I.H., Extr

Journal: Genes & development

VOLUME: 20

Page Numbers: 3174-84

Journal Abbreviation: Genes Dev.

ISSN: 0890-9369

DAY: 3

MONTH: 11

YEAR: 2006

Endotoxic shock in AUF1 knockout mice mediated by failure to degrade proinflammatory cytokine mRNAs. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 8711660

Endotoxic shock in AUF1 knockout mice mediated by failure to degrade proinflammatory cytokine mRNAs. Keywords Mesh Terms:

KEYWORDS: Tumor Necrosis Factor-alpha

MESH TERMS: metabolism

Chemical & Substance for Abstract: Endotoxic shock in AUF1 knockout mice mediated by failure to degrade proinflammatory cytokine mRNAs. Information

Substance Name: hnRNP D0

Registry Number: 0

Grant and Affiliation Information for Endotoxic shock in AUF1 knockout mice mediated by failure to degrade proinflammatory cytokine mRNAs.

AFFILIATION: Department of Microbiology, New York University School of Medicine, New York, New York 10016, USA.

Country: United States

AGENCY: United States NIGMS

GRANT: GM60428

ACRONYM: GM

MEDLINETA: Genes Dev

REFSOURCE:

DATABASENAME:

ACCESSION NUMBER:

Number Hits: 0

Endotoxic shock in AUF1 knockout mice mediated by failure to degrade proinflammatory cytokine mRNAs Related Publications

• A superconductive undulator with a period length of 3.8 mm.
• Abstinence and acceptance? The problematic relationship between the German abstinence paradigm, low-threshold oriented drug work, and methadone.
• Acarbose, a pseudooligosaccharide, is transported but not metabolized by the maltose-maltodextrin system of Escherichia coli.
• Akt and FOXO dysregulation contribute to infection-induced wasting in Drosophila.
• All my rights.
• Articular cartilage repair by gene therapy using growth factor-producing mesenchymal cells.
• Bone regeneration in critical size defects by cell-mediated BMP-2 gene transfer: a comparison of adenoviral vectors and liposomes.
• Calcium transients and intramembrane charge movement in skeletal muscle fibres.
• Cell size and Cln-Cdc28 complexes mediate entry into meiosis by modulating cell growth.
• Chest CT findings in pediatric Wegener's granulomatosis.
• Development of ATD Installation Procedures Based on Rear-Seat Occupant Postures.
• Does attention alter appearance?
• Dynamic modulation of upper airway function during sleep: a novel single-breath method.
• Effect of electrostatic interactions on binding and retention of DNA oligomers to PNA liposomes assessed by FRET measurements.
• Effects of nicotinic therapies on attention and executive functions in chronic low-dose MPTP-treated monkeys.
• Endotoxic shock in AUF1 knockout mice mediated by failure to degrade proinflammatory cytokine mRNAs.
• Estimating infant head injury criteria and impact response using crash reconstruction and finite element modeling.
• Evidence for cortical dysfunction and widespread manganese accumulation in the nonhuman primate brain following chronic manganese exposure: a 1H-MRS and MRI study.
• Fibroblast-mediated delivery of growth factor complementary DNA into mouse joints induces chondrogenesis but avoids the disadvantages of direct viral gene transfer.
• Influence of day of collection on recovery rate in mature cycling mares.
• Influence of intensive embryo collection on subsequent embryo production.
• Influence of vesicle curvature on fluorescence relaxation kinetics of fluorophores.
• Metabolic and hormonal control of the desire for food and sex: implications for obesity and eating disorders.
• Nigrostriatal dopamine system dysfunction and subtle motor deficits in manganese-exposed non-human primates.
• Perceived barriers to walking for physical activity.
• Shigella as a foodborne pathogen and current methods for detection in food.
• The effects of tethering rear -facing child restraint systems on atd responses.
• The tolerance of the human hip to dynamic knee loading.
• [Evidence-based guidelines - what is the present situation?]
• [Innovative imaging in urology: fascination and future : Yesterday, today, and tomorrow.]