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Silver nanoparticles modify VEGF signaling pathway and mucus hypersecretion in allergic airway inflammation.

ABSTRACT: The anti-inflammatory action of silver nanoparticles (NPs) has been reported in a murine model of asthma in a previous study. But more specific mechanisms of silver NPs in an attenuation of allergic airway inflammation have not yet been established. Vascular and mucous changes are believed to contribute largely in pathophysiology in asthma. Among various factors related to vascular changes, vascular endothelial growth factor (VEGF) plays a pivotal role in vascular changes in asthma. Mucin proteins MUC5AC and MUC5B have been implicated as markers of goblet cell metaplasia in lung pathologies. The aim of this study was to investigate the effects of silver NPs on VEGF signaling pathways and mucus hypersecretion. Ovalbumin (OVA)-inhaled female BALBc mice were used to evaluate the role of silver NPs and the related molecular mechanisms in allergic airway disease. In this study, with an OVA-induced murine model of allergic airway disease, it was found that the increased levels of hypoxia-inducible factor (HIF)-1?, VEGF, phosphatidylinositol-3 kinase (PI3K) and phosphorylated-Akt levels, and mucous glycoprotein expression (Muc5ac) in lung tissues were substantially decreased by the administration of silver NPs. In summary, silver NPs substantially suppressed mucus hypersecretion and PI3K/HIF-1?/VEGF signaling pathway in an allergic airway inflammation.

SUBMITTER: Jang S

PROVIDER: S-EPMC3310409 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

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Silver nanoparticles modify VEGF signaling pathway and mucus hypersecretion in allergic airway inflammation.

Jang Sunhyae S Park Ji Won JW Cha Hye Rim HR Jung Sun Young SY Lee Jeong Eun JE Jung Sung Soo SS Kim Ju Ock JO Kim Sun Young SY Lee Choong Sik CS Park Hee Sun HS

International journal of nanomedicine 20120314

The anti-inflammatory action of silver nanoparticles (NPs) has been reported in a murine model of asthma in a previous study. But more specific mechanisms of silver NPs in an attenuation of allergic airway inflammation have not yet been established. Vascular and mucous changes are believed to contribute largely in pathophysiology in asthma. Among various factors related to vascular changes, vascular endothelial growth factor (VEGF) plays a pivotal role in vascular changes in asthma. Mucin protei ...[more]

PMID: 22457593

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Project description:IntroductionAsthma with airway mucus hypersecretion is an inadequately characterized variant of asthma. While several studies have reported that hypersecreting patients may carry genetic variants in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, many of those studies have been questioned for their numerous limitations and contradictory results.Objectives(1) To determine the presence of genetic variants of the CFTR gene in patients with asthma with and without airway mucus hypersecretion. (2) To identify the clinical, inflammatory and functional characteristics of the asthma phenotype with airway mucus hypersecretion.MethodComparative multicentre cross-sectional descriptive study that included 100 patients with asthma (39 hypersecretors and 61 non-hypersecretors). Asthmatic hypersecretion was defined as the presence of cough productive of sputum on most days for at least 3 months in 2 successive years. The patients were tested for fractional exhaled nitric oxide, spirometry, induced sputum cell count, total immunoglobulin E (IgE), peripheral blood eosinophil count, C-reactive protein, blood fibrinogen and blood albumin and underwent a skin prick test. Asthma control and quality of life were assessed by the Asthma Control Test and Mini Asthma Quality of Life questionnaires, respectively. Blood DNA samples were collected from the patients and next-generation sequencing using a MiSeq sequencer and the Illumina platform was used for the CFTR gene analysis.ResultsGenetic differences were observed in the c.1680-870T>A polymorphism of the CFTR gene, significantly more evident in hypersecretors than in non-hypersecretors: 78.94% vs. 59.32% in the majority allele and 21.05% vs. 40.67% in the minority allele (p = 0.036). Clinically, asthma hypersecretors compared to non-hypersecretors were older (57.4 years vs. 49.4 years; p = 0.004); had greater asthma severity (58.9% vs. 23.7%; p = 0.005); experienced greater airway obstruction (FEV1/FVC% 64.3 vs. 69.5; p = 0.041); had poorer asthma control (60% vs. 29%; p = 0.021); had lower IgE levels (126.4 IU/mL vs. 407.6 IU/mL; p = 0.003); and were less likely to have a positive prick test (37.5% vs. 68.85%; p = 0.011).ConclusionThe results suggest that patients with asthma and with mucus hypersecretion (1) may have a different phenotype and disease mechanism produced by an intronic polymorphism in the CFTR gene (NM_000492.3:c.1680-870T>A), and (2) may have a poorer clinical outcome characterized by severe disease and poorer asthma control with a non-allergic inflammatory phenotype.

Project description:BackgroundLianhua Qingke (LHQK) is an effective traditional Chinese medicine used for treating acute tracheobronchitis. In this study, we evaluated the effectiveness of LHQK in managing airway mucus hypersecretion in the acute exacerbation of chronic obstructive pulmonary disease (AECOPD).MethodsThe AECOPD model was established by subjecting male Wistar rats to 12 weeks of cigarette smoke (CS) exposure (80 cigarettes/day, 5 days/week for 12 weeks) and intratracheal lipopolysaccharide (LPS) exposure (200 μg, on days 1, 14, and 84). The rats were divided into six groups: control (room air exposure), model (CS + LPS exposure), LHQK (LHQK-L, LHQK-M, and LHQK-H), and a positive control group (Ambroxol). H&E staining, and AB-PAS staining were used to evaluate lung tissue pathology, inflammatory responses, and goblet cell hyperplasia. RT-qPCR, immunohistochemistry, immunofluorescence and ELISA were utilized to analyze the transcription, expression and secretion of proteins related to mucus production in vivo and in the human airway epithelial cell line NCI-H292 in vitro. To predict and screen the active ingredients of LHQK, network pharmacology analysis and NF-κB reporter system analysis were employed.ResultsLHQK treatment could ameliorate AECOPD-triggered pulmonary structure damage, inflammatory cell infiltration, and pro-inflammatory cytokine production. AB-PAS and immunofluorescence staining with CCSP and Muc5ac antibodies showed that LHQK reduced goblet cell hyperplasia, probably by inhibiting the transdifferentiation of Club cells into goblet cells. RT-qPCR and immunohistochemistry of Muc5ac and APQ5 showed that LHQK modulated mucus homeostasis by suppressing Muc5ac transcription and hypersecretion in vivo and in vitro, and maintaining the balance between Muc5ac and AQP5 expression. Network pharmacology analysis and NF-κB luciferase reporter system analysis provided insights into the active ingredients of LHQK that may help control airway mucus hypersecretion and regulate inflammation.ConclusionLHQK demonstrated therapeutic effects in AECOPD by reducing inflammation, suppressing goblet cell hyperplasia, preventing Club cell transdifferentiation, reducing Muc5ac hypersecretion, and modulating airway mucus homeostasis. These findings support the clinical use of LHQK as a potential treatment for AECOPD.

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Silver nanoparticles modify VEGF signaling pathway and mucus hypersecretion in allergic airway inflammation.

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Silver nanoparticles modify VEGF signaling pathway and mucus hypersecretion in allergic airway inflammation.

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