Inhibition of neutrophil elastase attenuates airway hyperresponsiveness and inflammation in a mouse model of secondary allergen challenge: neutrophil elastase inhibition attenuates allergic airway responses

Published on Jan 24, 2013in Respiratory Research3.924
· DOI :10.1186/1465-9921-14-8
Hikari Koga8
Estimated H-index: 8
(Okayama University),
Nobuaki Miyahara33
Estimated H-index: 33
(Okayama University)
+ 8 AuthorsArihiko Kanehiro25
Estimated H-index: 25
(Okayama University)
Background Chronic asthma is often associated with neutrophilic infiltration in the airways. Neutrophils contain elastase, a potent secretagogue in the airways, nonetheless the role for neutrophil elastase as well as neutrophilic inflammation in allergen-induced airway responses is not well defined. In this study, we have investigated the impact of neutrophil elastase inhibition on the development of allergic airway inflammation and airway hyperresponsiveness (AHR) in previously sensitized and challenged mice.
📖 Papers frequently viewed together
419 Citations
12 Authors (Makoto Kudo, ..., Dean Sheppard)
329 Citations
4 Citations
#1Masato Yashiro (Okayama University)H-Index: 10
#2Hirokazu TsukaharaH-Index: 39
Last. Tsuneo Morishima (Okayama University)H-Index: 58
view all 13 authors...
Objectives: Influenza virus infections can cause severe acute lung injury leading to significant morbidity and mortality. Thioredoxin-1 is a redox-active defensive protein induced in response to stress conditions. Animal experiments have revealed that thioredoxin-1 has protective effects against various severe disorders. This study was undertaken to evaluate the protective effects of recombinant human thioredoxin-1 administration on influenza A virus (H1N1)-induced acute lung injury in mice. Des...
29 CitationsSource
Placental growth factor (PlGF) and its receptor vascular endothelial growth factor receptor 1 (VEGFR1) play an important role in pathological conditions related to angiogenesis, vascular leakage, and inflammation. This study investigated their contributions to inflammation and the formation of edema in allergic asthma. The expression of PlGF and VEGFR1 was measured in induced sputum of patients with asthma (n = 11) and healthy subjects (n = 11), and in bronchial biopsies of house dust mite (HDM)...
19 CitationsSource
#1Lisa Wood (University of Newcastle)H-Index: 77
#2Katherine J. Baines (University of Newcastle)H-Index: 33
Last. Peter G. Gibson (University of Newcastle)H-Index: 119
view all 5 authors...
Background The role of systemic inflammation in asthma is unclear. The aim of this study was to compare systemic inflammation in subjects with stable asthma, categorized by airway inflammatory phenotype, with healthy control subjects. Methods Adults with stable asthma (n = 152) and healthy control subjects (n = 83) underwent hypertonic saline challenge and sputum induction. Differential leukocyte counts were performed on selected sputum. Plasma high-sensitivity C-reactive protein (CRP), IL-6, an...
205 CitationsSource
#1Takeshi Nabe (Kyoto Pharmaceutical University)H-Index: 25
#2Ayumu Ikedo (Kyoto Pharmaceutical University)H-Index: 3
Last. David D. Chaplin (UAB: University of Alabama at Birmingham)H-Index: 66
view all 10 authors...
Abstract It has been suggested that interleukin (IL)-10 exerts immunosuppressive effects on allergic inflammation, including asthma, mainly through inhibition of Th2 cell-mediated eosinophilic airway inflammation. In a model of experimental asthma utilizing multiple intratracheal antigen challenges in sensitized mice, IL-10 production as well as eosinophilia and neutrophilia in the lung were induced by the multiple challenges. In this study, we set out to reveal the cellular source of endogenous...
22 CitationsSource
#1Yasuko FuchimotoH-Index: 1
1 Citations
#1Katherine J. Baines (University of Newcastle)H-Index: 33
#2Jodie L. SimpsonH-Index: 57
Last. Peter G. GibsonH-Index: 119
view all 5 authors...
Background The well-characterised airway inflammatory phenotypes of asthma include eosinophilic, neutrophilic, mixed eosinophilic/neutrophilic and paucigranulocytic asthma, identified based on the proportion of sputum granulocytes. Systemic inflammation is now recognised as an important part of some airway diseases, but the involvement of systemic inflammation in the pathogenesis of airway inflammatory phenotypes of asthma remains unknown. Methods Induced sputum samples and peripheral blood were...
53 CitationsSource
#1Koichi WasedaH-Index: 9
#2Nobuaki Miyahara (RMIT: RMIT University)H-Index: 33
Last. Erwin W. Gelfand (University of Colorado Denver)H-Index: 113
view all 11 authors...
Most of the studies investigating the effectiveness of blocking the leukotriene B4 (LTB4) receptor 1 (BLT1) have been performed in models of primary or acute allergen challenge. The role of the LTB4-BLT1 pathway in secondary challenge models, where airway hyperresponsiveness (AHR) and airway inflammation have been established, has not been defined. We investigated the effects of blocking BLT1 on early- and late-phase development of AHR and airway inflammation in previously sensitized and challen...
14 CitationsSource
#1Yasuko Fuchimoto (Okayama University)H-Index: 9
#2Arihiko KanehiroH-Index: 25
Last. Mitsune TanimotoH-Index: 68
view all 11 authors...
Chemokine receptor (CCR) 5 is expressed on dendritic cells, macrophages, CD8 cells, memory CD4 T cells, and stromal cells, and is frequently used as a marker of T helper type 1 cells. Interventions that abrogate CCR5 or interfere with its ligand binding have been shown to alter T helper type 2–induced inflammatory responses. The role of CCR5 on allergic airway responses is not defined. CCR5-deficient (CCR5−/−) and wild-type (CCR5+/+) mice were sensitized and challenged with ovalbumin (OVA) and a...
14 CitationsSource
#1Kirstin M. HeutinckH-Index: 13
Last. Ajda T. RowshaniH-Index: 24
view all 5 authors...
Serine proteases form a large family of protein-cleaving enzymes that play an essential role in processes like blood coagulation, apoptosis and inflammation. Immune cells express a wide variety of serine proteases such as granzymes in cytotoxic lymphocytes, neutrophil elastase, cathepsin G and proteinase 3 in neutrophils and chymase and tryptase in mast cells. Regulation of proteolysis induced by these serine proteases is essential to prevent self-induced damage. Hence, there are specialized ser...
174 CitationsSource
#1Sharmilee M. Nyenhuis (UIC: University of Illinois at Chicago)H-Index: 15
#2Elizabeth A. Schwantes (UW: University of Wisconsin-Madison)H-Index: 11
Last. Sameer K. Mathur (UW: University of Wisconsin-Madison)H-Index: 24
view all 4 authors...
Asthma in the elderly has been inadequately studied. The age demographic >65 years old is the fastest growing in the United States, and asthma in the elderly population is frequently underdiagnosed and undertreated(1). Furthermore, elderly asthmatics also have a higher rate of severe exacerbations, emergency department visits, and hospitalizations than younger asthmatics which represents significant disease impairment and risk(2). The airway inflammation in older asthma subjects differs from you...
47 CitationsSource
Cited By41
#1Hamed Janbazacyabar (UU: Utrecht University)H-Index: 1
#2Marthe van Daal (UU: Utrecht University)
Last. Saskia Braber (UU: Utrecht University)H-Index: 23
view all 0 authors...
Cigarette smoke exposure during pregnancy and lactation is associated with adverse pregnancy outcomes. Here, we investigated the effects of maternal smoke exposure on pregnancy and offspring immunity and explored whether, epidermal growth factor (EGF), an important growth-promoting factor in human colostrum and milk, might be a possible missing link in maternal smoke exposure and changes in infants’ immune responses. Pregnant BALB/c mice were exposed to either cigarette smoke or air during gesta...
#1Holly R. Keir (Dund.: University of Dundee)H-Index: 8
#2James D. Chalmers (Dund.: University of Dundee)H-Index: 67
Bronchiectasis is a complex, heterogeneous disorder defined by both a radiological abnormality of permanent bronchial dilatation and a clinical syndrome. There are multiple underlying causes including severe infections, mycobacterial disease, autoimmune conditions, hypersensitivity disorders, and genetic conditions. The pathophysiology of disease is understood in terms of interdependent concepts of chronic infection, inflammation, impaired mucociliary clearance, and structural lung damage. Neutr...
#1Małgorzata Proboszcz (Medical University of Warsaw)H-Index: 7
#2Krzysztof Goryca (University of Warsaw)H-Index: 2
Last. Magdalena Paplińska-Goryca (Medical University of Warsaw)H-Index: 7
view all 7 authors...
Purpose null Asthma and chronic obstructive pulmonary disease (COPD) are complex and heterogeneous inflammatory diseases. We sought to investigate distinct disease profiles based on clinical, cellular and molecular data from patients with mild-to-moderate obstructive pulmonary diseases. null Patients and methods null Patients with mild-to-moderate allergic asthma (n=30) and COPD (n=30) were prospectively recruited. Clinical characteristics and induced sputum were collected. In total, 35 mediator...
#1Jia Wenxiu (Hebei Medical University)
#2Yang Mingyue (Hebei Medical University)
Last. Stephan R. Targan (Cedars-Sinai Medical Center)H-Index: 116
view all 11 authors...
Background and Aims. Recent evidences reveal that epithelial to mesenchymal transition (EMT) exacerbates the process of intestinal fibrosis. Tumor necrosis factor-like ligand 1A (TL1A) is a member of the tumor necrosis family (TNF), which can take part in the development of colonic inflammation and fibrosis by regulating immune response or inflammatory factors. The purpose of this study was to elucidate the possible contribution of TL1A in onset and progression of intestinal inflammation and fib...
#1Shan Guan (Third Military Medical University)
view all 4 authors...
#1Helena Crisford (University of Birmingham)H-Index: 3
#2Elizabeth Sapey (University of Birmingham)H-Index: 26
Last. Jodie L. Simpson (University of Newcastle)H-Index: 57
view all 7 authors...
Airway inflammation plays a key role in asthma pathogenesis but is heterogeneous in nature. There has been significant scientific discovery with regard to type 2-driven, eosinophil-dominated asthma, with effective therapies ranging from inhaled corticosteroids to novel biologics. However, studies suggest that approximately 1 in 5 adults with asthma have an increased proportion of neutrophils in their airways. These patients tend to be older, have potentially pathogenic airway bacteria and do not...
1 CitationsSource
#1Rongjun Wan (CSU: Central South University)H-Index: 2
#2Juan Jiang (CSU: Central South University)H-Index: 4
Last. Yuanyuan Li (CSU: Central South University)H-Index: 7
view all 9 authors...
Neutrophilic asthma (NA) is a distinct airway inflammation disease with prominent neutrophil infiltration. The role played by neutrophil extracellular traps (NETs) in NA, however, is quite unclear. This study was based on the hypothesis that NETs are responsible for the second neutrophil wave and therefore contribute significantly to inflammation. The proinflammatory effects of NETs were evaluated in vitro and in vivo. Formation of NETs and neutrophil swarming was seen in a mouse model of NA. Ad...
4 CitationsSource
#1Naohiro Oda (Okayama University)H-Index: 8
#2X. Nobuaki Miyahara (RMIT: RMIT University)H-Index: 1
Last. Yoshinobu Maeda (Okayama University)H-Index: 29
view all 11 authors...
Neuropeptide Y (NPY) is a neurotransmitter that is widely expressed in the brain and peripheral nervous system. Various immune cells express the NPY Y1 receptor. NPY modulates these cells via its Y...
7 CitationsSource
#1Hirohisa Ogawa (University of Tokushima)H-Index: 19
#2Masahiko Azuma (University of Tokushima)H-Index: 8
Last. Koichi Tsuneyama (University of Tokushima)H-Index: 78
view all 8 authors...
BACKGROUND: Bronchial asthma is traditionally characterized by chronic allergic inflammation, including eosinophilia and elevated Th2 cytokines. Recently, IL-17-derived neutrophil infiltration was shown to correlate with asthma severity and airway remodelling. OBJECTIVE: To investigate the role of IL-17-derived neutrophils in airway remodelling in chronic bronchial asthma. METHODS: We utilized house dust mite antigen-induced mouse models of asthma. Intranasal sensitization and chronic antigen ch...
6 CitationsSource
#2Renaud LouisH-Index: 58
Last. Thomas MarichalH-Index: 27
view all 4 authors...
The contribution of neutrophils to asthma pathogenesis has been mainly studied in the context of non-allergic neutrophilic asthma. However, neutrophils can also be rapidly recruited and are largely present in the airways of allergic eosinophilic asthmatic patients. Under these circumstances, they possess specific phenotypic features distinguishing them from resting blood neutrophils and are endowed with particular functions. The exact contribution of neutrophils to allergic asthma pathogenesis i...
20 CitationsSource