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  5. Gene Transcription and Oxidant Injury in Heaves
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Gene Transcription and Oxidant Injury in Heaves

Author(s):
Lekeux P. and
Kirschvink N.
In: WEAS - Symposium - Scotland, 2001 by World Equine Airway Society
Updated:
JUL 23, 2001
Languages:
  • EN
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    Equine heaves is an inflammatory condition of the airways, in which an hypersensitivity response to inhaled antigens is involved. Because inflammation associated with hypersensitivity results from an exaggerated expression of inflammatory genes, recent studies aimed at identifying the mechanisms implicated in this inappropriate inflammatory gene induction in heaves.

    Main inflammatory genes encode (a) proinflammatory cytokines, including interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α), which amplify pulmonary inflammation, (b) chemokines, such as interleukin-8 (IL-8), macrophage inflammatory protein-1α (MIP-1α), macrophage chemotactic protein-3 (MCP-3), RANTES (Regulated on Activation Normal T-cell Expressed and Secreted) and eotaxin, which are chemotactic for leukocytes, (c) adhesion factors, including intracellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and E- selectin, which play a cardinal role in leukocyte recruitment, margination, diapedesis and transepithelial migration, and (d) inflammatory enzymes, such as cytosolic phospholipase A2 (cPLA2), inducible cyclooxygenase (COX-2) and inducible nitric oxide synthase (iNOS), which generate inflammatory mediators. All these inflammatory genes have been shown to contain κB sites for the transcription factor, nuclear factor κB (NF-κB), within their promoter or enhancer and therefore to depend on NF-κB for their expression, suggesting that this transcription factor could play a key role in the pathophysiology of equine heaves. Therefore, our studies focused on the importance of NF-κB activity in this disease.

    NF-κB complexes are composed of five distinct DNA-binding subunits, called p50, p52, p65/RelA, c-Rel/Rel, and RelB. Although the most common NF-κB complex is an heterodimer composed of the p65 and p50 subunits, the different family members can associate in various homo- or heterodimers through a highly conserved N-terminal sequence, called Rel homology domain. Inactive NF-κB complexes are present in the cytosol associated with inhibitory proteins of the IκB family, including IκB-α, IκB-β, IκB-ε, p100 and p105. Following various stimuli, such as viruses, bacteria, prooxidants, and proinflammatory cytokines, IκB proteins are first phosphorylated, and then rapidly degraded by the proteasome, allowing NF-κB nuclear translocation and transcriptional initiation of NF-κB-dependent genes.  [...]

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    About

    How to reference this publication (Harvard system)?

    Lekeux, P. and Kirschvink, N. (2001) “Gene Transcription and Oxidant Injury in Heaves”, WEAS - Symposium - Scotland, 2001. Available at: https://www.ivis.org/library/weas/weas-symposium-scotland-2001/gene-transcription-and-oxidant-injury-heaves (Accessed: 01 October 2023).

    Author(s)

    • Pierre Lekeux

      Lekeux P.

      Professor
      DVM PhD Dipl ECVPT
      Department of Physiology and Sport Medicine, Faculty of Veterinary Medicine, University of Liège
      Read more about this author
    • Kirschvink N.

      DVM PhD
      Département des Sciences Fonctionnelles, Faculty of Veterinary Medicine, University of Liège
      Read more about this author

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    The WEAS brings together the leading equine airway researchers from around the world to present the latest knowledge and research and exchange experiences and information on diagnosing and treating (both medically and surgically) respiratory diseases in horses. About 100 participants from 23 countries attended WEAS 2017, where researchers presented more than 70 oral and poster abstracts.

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