title: Pituitary Adenylate Cyclase-Activating Polypeptide Reverses Ammonium Metavanadate-Induced Airway Hyperresponsiveness in Rats.
abstract: The rate of atmospheric vanadium is constantly increasing due to fossil fuel combustion. This environmental pollution favours vanadium exposure in particular to its vanadate form, causing occupational bronchial asthma and bronchitis. Based on the well admitted bronchodilator properties of the pituitary adenylate cyclase-activating polypeptide (PACAP), we investigated the ability of this neuropeptide to reverse the vanadate-induced airway hyperresponsiveness in rats. Exposure to ammonium metavanadate aerosols (5 mg/m(3)/h) for 15 minutes induced 4 hours later an array of pathophysiological events, including increase of bronchial resistance and histological alterations, activation of proinflammatory alveolar macrophages, and increased oxidative stress status. Powerfully, PACAP inhalation (0.1 mM) for 10 minutes alleviated many of these deleterious effects as demonstrated by a decrease of bronchial resistance and histological restoration. PACAP reduced the level of expression of mRNA encoding inflammatory chemokines (MIP-1α, MIP-2, and KC) and cytokines (IL-1α and TNF-α) in alveolar macrophages and improved the antioxidant status. PACAP reverses the vanadate-induced airway hyperresponsiveness not only through its bronchodilator activity but also by counteracting the proinflammatory and prooxidative effects of the metal. Then, the development of stable analogs of PACAP could represent a promising therapeutic alternative for the treatment of inflammatory respiratory disorders.
authors.affiliation: Laboratory of Integrated Physiology, Science Faculty of Bizerte, Carthage University, 7021 Zarzouna, Tunisia ; National Institute of Health and Medical Research (INSERM), U982, 76821 Mont-Saint-Aignan Cedex, France ; Institute for Research and Innovation in Biomedicine (IRIB), Normandy University, 76821 Mont-Saint-Aignan Cedex, France ; Laboratory of Neuronal and Neuroendocrine Differentiation and Communication, Rouen University, 76821 Mont-Saint-Aignan Cedex, France.
authors.forename: Mounira
authors.initials: M
authors.lastname: Tlili
authors.affiliation: Laboratory of Physiology and Functional Exploration, CHU Farhat Hached, 4000 Sousse, Tunisia.
authors.forename: Sonia
authors.initials: S
authors.lastname: Rouatbi
authors.affiliation: Laboratory of Pathologic Anatomy, CHU Farhat Hached, 4000 Sousse, Tunisia.
authors.forename: Badreddine
authors.initials: B
authors.lastname: Sriha
authors.affiliation: Laboratory of Integrated Physiology, Science Faculty of Bizerte, Carthage University, 7021 Zarzouna, Tunisia.
authors.forename: Khémais
authors.initials: K
authors.lastname: Ben Rhouma
authors.affiliation: Laboratory of Integrated Physiology, Science Faculty of Bizerte, Carthage University, 7021 Zarzouna, Tunisia.
authors.forename: Mohsen
authors.initials: M
authors.lastname: Sakly
authors.affiliation: National Institute of Health and Medical Research (INSERM), U982, 76821 Mont-Saint-Aignan Cedex, France ; Institute for Research and Innovation in Biomedicine (IRIB), Normandy University, 76821 Mont-Saint-Aignan Cedex, France ; Laboratory of Neuronal and Neuroendocrine Differentiation and Communication, Rouen University, 76821 Mont-Saint-Aignan Cedex, France.
authors.forename: David
authors.initials: D
authors.lastname: Vaudry
authors.affiliation: National Institute of Health and Medical Research (INSERM), U982, 76821 Mont-Saint-Aignan Cedex, France ; Institute for Research and Innovation in Biomedicine (IRIB), Normandy University, 76821 Mont-Saint-Aignan Cedex, France ; Laboratory of Neuronal and Neuroendocrine Differentiation and Communication, Rouen University, 76821 Mont-Saint-Aignan Cedex, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Wurtz
authors.affiliation: Laboratory of Integrated Physiology, Science Faculty of Bizerte, Carthage University, 7021 Zarzouna, Tunisia.
authors.forename: Olfa
authors.initials: O
authors.lastname: Tebourbi
mesh_terms: D000280:Administration, Inhalation; D000336:Aerosols / Q000737:chemistry; D000818:Animals; D054405:Chemokine CCL3 / Q000235:genetics / Q000378:metabolism; D054426:Chemokine CXCL2 / Q000235:genetics / Q000378:metabolism; D053582:Interleukin-1alpha / Q000235:genetics / Q000378:metabolism; D008168:Lung / Q000378:metabolism / Q000473:pathology; D016676:Macrophages, Alveolar / Q000166:cytology / Q000378:metabolism; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D060888:Real-Time Polymerase Chain Reaction; D012130:Respiratory Hypersensitivity / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism; D014638:Vanadates / Q000633:toxicity
chemical_list: D000336:Aerosols; C515429:CCL3 protein, human; D054405:Chemokine CCL3; D054426:Chemokine CXCL2; D053582:Interleukin-1alpha; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D014409:Tumor Necrosis Factor-alpha; D014638:Vanadates; C101036:ammonium metavanadate