title: An inactivated Pseudomonas aeruginosa medicament inhibits airway allergic inflammation and improves epithelial functions.
abstract: The features of asthma are airway hyperresponsiveness (AHR), excess production of Th2 cytokines, and eosinophil accumulation in the lungs. To investigate the antiasthmatic potential of an inactivated Pseudomonas aeruginosa medicament (PPA), as well as the underlying mechanism involved, we studied the effects of PPA on airway and epithelial functions. Airway resistance, cell enumeration, and IL-4, IFN-γ, and IL-17 secretion in bronchoalveolar lavage fluid were assayed on an OVA-sensitized AHR animal model. Flow cytometry was used to observe the effects of PPA on cell proliferation, real-time PCR was used to test the expressions of toll like receptor 4 and 5, and Th17 signal molecules Act1, NF-kB negative regulator A20, and western blot were used to detect NF-kB expression on cultured human bronchial epithelial cells (BECs). PPA-treated animals had suppressed airway resistance, eosinophil and lymphocytes infiltration, and IL-4 and IL-17 secretion. PPA can stimulate toll-like receptor-4 and 5 expressions, promote cell proliferation in normal and OVA-treated BECs, significantly decrease Act1 and NF-kB, and increase A20 expression in BECs treated by OVA. Our data suggest the therapeutic mechanism by which PPA effectively treats allergic inflammation on reductions of airway responsiveness, eosinophil infiltration, IL-4 and IL-17 secretion, and improvements of epithelial functions.
authors.affiliation: Department of Basic Medicine, Xiangya School of Medicine, Central South University, Changsha, 410078, Hunan, China.
authors.forename: Yurong
authors.initials: Y
authors.lastname: Tan
authors.affiliation: Department of Basic Medicine, Xiangya School of Medicine, Central South University, Changsha, 410078, Hunan, China.
authors.forename: Huijun
authors.initials: H
authors.lastname: Liu
authors.affiliation: Department of Basic Medicine, Xiangya School of Medicine, Central South University, Changsha, 410078, Hunan, China.
authors.forename: Huihui
authors.initials: H
authors.lastname: Yang
authors.affiliation: Department of Basic Medicine, Xiangya School of Medicine, Central South University, Changsha, 410078, Hunan, China.
authors.forename: Lili
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Basic Medicine, Xiangya School of Medicine, Central South University, Changsha, 410078, Hunan, China. xiaoqun1988@xysm.net.
authors.forename: Xiaoqun
authors.initials: X
authors.lastname: Qin
mesh_terms: D000403:Airway Resistance / Q000502:physiology; D000818:Animals; D001980:Bronchi / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D016535:Bronchial Hyperreactivity / Q000382:microbiology* / Q000628:therapy*; D048708:Cell Growth Processes / Q000502:physiology; D002478:Cells, Cultured; D018031:Connexin 43 / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D020381:Interleukin-17 / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D010446:Peptide Fragments / Q000378:metabolism; D011550:Pseudomonas aeruginosa / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020545:Respiratory Mucosa / Q000382:microbiology / Q000473:pathology; D058504:Th17 Cells / Q000378:metabolism; D051193:Toll-Like Receptors / Q000378:metabolism; D014162:Transfection; D000072598:Tumor Necrosis Factor alpha-Induced Protein 3
chemical_list: C541130:ACT1 protein; D018031:Connexin 43; D004268:DNA-Binding Proteins; D020381:Interleukin-17; D016328:NF-kappa B; D010446:Peptide Fragments; D051193:Toll-Like Receptors; D015847:Interleukin-4; D007371:Interferon-gamma; C000602677:TNFAIP3 protein, rat; D000072598:Tumor Necrosis Factor alpha-Induced Protein 3