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Clin Sci (Lond). 2016 Nov 1;130(21):1939-54. doi: 10.1042/CS20160530. Epub 2016 Aug 22.

Glufosinate aerogenic exposure induces glutamate and IL-1 receptor dependent lung inflammation.

Author information

1
UMR7355, CNRS, 45 071 Orleans cedex 2, France INEM, Experimental and Molecular Immunology and Neurogenetics, University of Orleans, 3b rue de la Férollerie, 45071 Orleans Cedex 2, France.
2
UMR7355, CNRS, 45 071 Orleans cedex 2, France INEM, Experimental and Molecular Immunology and Neurogenetics, University of Orleans, 3b rue de la Férollerie, 45071 Orleans Cedex 2, France Genetics Department, Regional Hospital, 14 Avenue de l'Hôpital, 45100 Orleans, France.
3
Louvain Centre for Toxicology and Applied Pharmacology (LTAP), Institut de Recherche Expérimentale et Clinique (IREC), Avenue E. Mounier, 53 bte B1.52.12, B-1200 Bruxelles, Belgium.
4
UMR7355, CNRS, 45 071 Orleans cedex 2, France INEM, Experimental and Molecular Immunology and Neurogenetics, University of Orleans, 3b rue de la Férollerie, 45071 Orleans Cedex 2, France celine.dubourg@cnrs-orleans.fr.

Abstract

Glufosinate-ammonium (GLA), the active component of an herbicide, is known to cause neurotoxicity. GLA shares structural analogy with glutamate. It is a powerful inhibitor of glutamine synthetase (GS) and may bind to glutamate receptors. Since these potentials targets of GLA are present in lung and immune cells, we asked whether airway exposure to GLA may cause lung inflammation in mice. A single GLA exposure (1 mg/kg) induced seizures and inflammatory cell recruitment in the broncho-alveolar space, and increased myeloperoxidase (MPO), inducible NO synthase (iNOS), interstitial inflammation and disruption of alveolar septae within 6-24 h. Interleukin 1β (IL-1β) was increased and lung inflammation depended on IL-1 receptor 1 (IL-1R1). We demonstrate that glutamate receptor pathway is central, since the N-methyl-D-aspartate (NMDA) receptor inhibitor MK-801 prevented GLA-induced lung inflammation. Chronic exposure (0.2 mg/kg 3× per week for 4 weeks) caused moderate lung inflammation and enhanced airway hyperreactivity with significant increased airway resistance. In conclusion, GLA aerosol exposure causes glutamate signalling and IL-1R-dependent pulmonary inflammation with airway hyperreactivity in mice.

KEYWORDS:

IL1β; glufosinate ammonium; glutamate receptors; inflammation; lung; pesticide

PMID:
27549113
DOI:
10.1042/CS20160530
[Indexed for MEDLINE]

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