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Linalool attenuates lung inflammation induced by Pasteurella multocida via activating Nrf-2 signaling pathway.

Abstract
Pasteurellosis caused by Pasteurella multocida manifest often as respiratory infection in farmed small ruminants. Although the incidence of pasteurellosis due to P. multocida mainly takes the form of pneumonia, there is limited information on host factors that play a role in disease pathogenesis in the milieu of host-pathogen interactions. Nuclear factor-erythroid 2 related factor 2 (Nrf-2), a critical regulator for various inflammatory and immune responses by controlling oxidative stress, may play an important role in the processes of inflammation induced by P. multocida. In this study, linalool, a natural compound of the essential oils in several aromatic plant species, elevated nuclear Nrf-2 protein translocation in the A549 lung cell line and in vivo. The P. multocida-induced pro-inflammatory cytokines expression was abrogated by Nrf-2 siRNA. Postponed treatment with linalool decreased lung neutrophil accumulation and enhanced clearance of P. multocida. Furthermore, linalool significantly increased the expression of antioxidant enzymes regulated by Nrf-2 and diminished lung tissue levels of several pro-inflammatory cytokines, including tumor necrosis factor α (TNF-α) and interleukin (IL)-6. In addition, animals treated with linalool had a marked improvement in survival. These findings have uncovered that linalool acts as a novel Nrf-2 activator for a novel therapeutic strategy in pathogen-mediated lung inflammation.
AuthorsQianchao Wu, Lijun Yu, Jiaming Qiu, Bingyu Shen, Di Wang, Lanan Wassy Soromou, Haihua Feng
JournalInternational immunopharmacology (Int Immunopharmacol) Vol. 21 Issue 2 Pg. 456-63 (Aug 2014) ISSN: 1878-1705 [Electronic] Netherlands
PMID24925757 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2014 Elsevier B.V. All rights reserved.
Chemical References
  • Acyclic Monoterpenes
  • Antioxidants
  • Interleukin-6
  • Monoterpenes
  • NF-E2-Related Factor 2
  • NFE2L2 protein, human
  • Oils, Volatile
  • Tumor Necrosis Factor-alpha
  • linalool
Topics
  • Acyclic Monoterpenes
  • Animals
  • Antioxidants (metabolism)
  • Cell Line, Tumor
  • Host-Pathogen Interactions
  • Interleukin-6 (metabolism)
  • Lung (drug effects, metabolism)
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Monoterpenes (pharmacology)
  • NF-E2-Related Factor 2 (metabolism)
  • Neutrophils (drug effects, metabolism)
  • Oils, Volatile (pharmacology)
  • Pasteurella Infections (drug therapy, metabolism)
  • Pasteurella multocida (drug effects)
  • Pneumonia (drug therapy, metabolism)
  • Signal Transduction (drug effects)
  • Tumor Necrosis Factor-alpha (metabolism)

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