Oncostatin M expression induced by bacterial triggers drives airway inflammatory and mucus secretion in severe asthma

2022 ◽  
Vol 14 (627) ◽  
Author(s):  
Sarah E. Headland ◽  
Hart S. Dengler ◽  
Daqi Xu ◽  
Grace Teng ◽  
Christine Everett ◽  
...  
Keyword(s):  
Airway Inflammation ◽  
Severe Asthma ◽  
Oncostatin M ◽  
Mucus Secretion ◽  
Mucus Hypersecretion

Bacterial-associated LPS drives oncostatin M–dependent airway inflammation and mucus hypersecretion in severe asthma.

scholarly journals Curcumin Attenuates Asthmatic Airway Inflammation and Mucus Hypersecretion Involving a PPARγ-Dependent NF-κB Signaling Pathway In Vivo and In Vitro

2019 ◽  
Vol 2019 ◽  
pp. 1-15 ◽  
Author(s):  
Tao Zhu ◽  
Zhihong Chen ◽  
Guihua Chen ◽  
Daoxin Wang ◽  
Shuo Tang ◽  
...  
Keyword(s):  
Airway Inflammation ◽  
Signaling Pathway ◽  
Underlying Mechanism ◽  
Binding Activity ◽  
Mucus Secretion ◽  
Mucus Hypersecretion ◽  
Asthmatic Airway ◽  
Dna Binding Activity

Asthma is characterized by airway inflammation and mucus hypersecretion. Curcumin possessed a potent anti-inflammatory property involved in the PPARγ-dependent NF-κB signaling pathway. Then, the aim of the current study was to explore the value of curcumin in asthmatic airway inflammation and mucus secretion and its underlying mechanism. In vivo, mice were sensitized and challenged by ovalbumin (OVA) to induce chronic asthma. Airway inflammation and mucus secretion were analyzed. In vitro, BEAS-2B cells were obtained. MCP-1, MUC5AC, and PPARγ expression and the phosphorylation of NF-κB p65 and NF-κB p65 DNA-binding activity were measured in both the lungs and BEAS-2B cells. shRNA-PPARγ was used to knock down PPARγ expression. We found that OVA-induced airway inflammation and mucus hypersecretion in mice, OVA and IL-4-induced upregulation of MCP-1 and MUC5AC, suppression of PPARγ, and activation and translocation of NF-κB p65 were notably improved by curcumin both in vivo and in vitro. Our data also showed that these effects of curcumin were significantly abrogated by shRNA-PPARγ. Taken together, our results indicate that curcumin attenuated OVA-induced airway inflammation and mucus hypersecretion in mice and suppressed OVA- and IL-4-induced upregulation of MCP-1 and MUC5AC both in vivo and in vitro, most likely through a PPARγ-dependent NF-κB signaling pathway.

scholarly journals Gekko gecko extract attenuates airway inflammation and mucus hypersecretion in a murine model of ovalbumin-induced asthma

2022 ◽  
Vol 282 ◽  
pp. 114574
Author(s):  
Hyeon Hwa Nam ◽  
Ji Hye Lee ◽  
Seung Mok Ryu ◽  
Sueun Lee ◽  
Sungyu Yang ◽  
...  
Keyword(s):  
Airway Inflammation ◽  
Murine Model ◽  
Gekko Gecko ◽  
Mucus Hypersecretion

scholarly journals Relationships between IL-17A and Macrophages or MUC5AC in Eosinophilic Chronic Rhinosinusitis and Proposed Pathological Significance

2012 ◽  
Vol 3 (2) ◽  
pp. ar.2012.3.0030 ◽  
Author(s):  
Noritsugu Ono ◽  
Takeshi Kusunoki ◽  
Katsuhisa Ikeda
Keyword(s):  
Airway Inflammation ◽  
Chronic Rhinosinusitis ◽  
Neutrophil Elastase ◽  
Nasal Polyps ◽  
Mucus Hypersecretion ◽  
Promotive Factors ◽  
Chemotactic Protein ◽  
Eosinophilic Chronic Rhinosinusitis ◽  
Semithin Sections ◽  
The Mean

Recently, some researchers have reported that macrophages and neutrophils were related to severe asthma. Mucus hypersecretion and persistent airway inflammation result from increased expression of mucin gene (MUC5AC). Eosinophilic chronic rhinosinusitis (ECRS) is considered as intractable rhinosinusitis. From the viewpoint of “one way one disease,” we examined whether ECRS is associated with infiltrating macrophages, neutrophils, their promotive factors, and MUC5AC. We examined 21 nasal polyps with CRS. Each specimen was fixed in 10% phosphate-buffered formalin, embedded in paraffin, processed routinely, and then prepared as semithin sections (3.5 μm). We immunohistochemically observed the macrophages by using CD68, neutrophils by using neutrophil elastase and the promotive factors, monocyte chemotactic protein (MCP) 1, IL-17A, and IL-8, in both ECRS and non-ECRS. The number of macrophages (CD68+ cells), IL-17A, and MUC5AC+ cells in ECRS were significantly greater than in non-ECRS. The mean number of MCP-1+ cells in ECRS was greater than that in non-ECRS, but not significantly. There was a significant correlation in all cases between IL-17A and macrophages or MUC5AC+ cells. Neither the numbers of neutrophils (positive cells for neutrophil elastase) nor the IL-8+ cells showed any significant differences between ECRS and non-ECRS. Our study suggested that infiltrating macrophages, IL-17A and MUC5AC, as well as eosinophils could have roles in the development of ECRS.

scholarly journals Bifidobacterium breve MRx0004 protects against airway inflammation in a severe asthma model by suppressing both neutrophil and eosinophil lung infiltration

2018 ◽  
Vol 8 (1) ◽  
Author(s):  
Emma J. Raftis ◽  
Margaret I. Delday ◽  
Philip Cowie ◽  
Seánín M. McCluskey ◽  
Mark D. Singh ◽  
...  
Keyword(s):  
Airway Inflammation ◽  
Severe Asthma ◽  
Bifidobacterium Breve ◽  
Asthma Model

Heme oxygenase attenuates allergen-induced airway inflammation and hyperreactivity in guinea pigs

2004 ◽  
Vol 287 (1) ◽  
pp. L26-L34 ◽  
Author(s):  
Abdelhamid Almolki ◽  
Camille Taillé ◽  
Gillian F. Martin ◽  
Peter J. Jose ◽  
Christine Zedda ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Airway Inflammation ◽  
Heme Oxygenase ◽  
Guinea Pigs ◽  
Protoporphyrin Ix ◽  
Airway Responsiveness ◽  
Mucus Secretion ◽  
Control Group ◽  
Repeated Administrations ◽  
Tin Protoporphyrin

Heme oxygenase (HO), the heme-degrading enzyme, has shown anti-inflammatory effects in several models of pulmonary diseases. HO is induced in airways during asthma; however, its functional role is unclear. Therefore, we evaluated the role of HO on airway inflammation [evaluated by bronchoalveolar lavage (BAL) cellularity and BAL levels of eotaxin, PGE2, and proteins], mucus secretion (evaluated by analysis of MUC5AC gene expression and periodic acid-Schiff staining), oxidative stress (evaluated by quantification of 4-hydroxynonenal adducts and carbonylated protein levels in lung homogenates), and airway responsiveness to histamine in ovalbumin (OVA)-sensitized and multiple aerosol OVA or saline-challenged guinea pigs (6 challenges, once daily, OVA group and control group, respectively). Airway inflammation, mucus secretion, oxidative stress, and responsiveness were significantly increased in the OVA group compared with the control group. HO upregulation by repeated administrations of hemin (50 mg/kg ip) significantly decreased airway responsiveness in control animals and airway inflammation, mucus secretion, oxidative stress, and responsiveness in OVA animals. These effects were reversed by the concomitant administration of the HO inhibitor tin protoporphyrin-IX (50 μmol/kg ip). Repeated administrations of tin protoporphyrin-IX alone significantly increased airway responsiveness in control animals but did not modify airway inflammation, mucus secretion, oxidative stress, and responsiveness in OVA animals. These results suggest that upregulation of the HO pathway has a significant protective effect against airway inflammation, mucus hypersecretion, oxidative stress, and hyperresponsiveness in a model of allergic asthma in guinea pigs.

scholarly journals The Role of Fucoidans Isolated from the Sporophylls of Undaria pinnatifida against Particulate-Matter-Induced Allergic Airway Inflammation: Evidence of the Attenuation of Oxidative Stress and Inflammatory Responses

Molecules ◽  
2020 ◽  
Vol 25 (12) ◽  
pp. 2869 ◽  
Author(s):  
Kalahe Hewage Iresha Nadeeka Madushani Herath ◽  
Hyo Jin Kim ◽  
Areum Kim ◽  
Chung Eui Sook ◽  
Boo-Yong Lee ◽  
...  
Keyword(s):  
Particulate Matter ◽  
Inflammatory Response ◽  
Airway Inflammation ◽  
Cell Activation ◽  
Inflammatory Responses ◽  
Undaria Pinnatifida ◽  
Mast Cell Activation ◽  
Cell Hyperplasia ◽  
Mucus Hypersecretion ◽  
Asthma Symptoms

Ambient particulate matter (PM) is a critical environment pollutant that promotes the onset and aggravation of respiratory diseases such as asthma through airway inflammation and hypersecretion of mucus. In this study, we aimed to identify the effects of fucoidans isolated from sporophylls of Undaria pinnatifida on asthma symptoms such as the inflammatory response and mucus secretion using a mouse model. Balb/c mice, intraperitoneally sensitized with ovalbumin (OVA, 10 μg) dissolved in 200 µL saline and 2 mg Al(OH)3, were exposed to PM (5 mg/m3) for 7 consecutive days. In parallel, along with PM exposure, we orally administrated fucoidans (100, 400 mg/Kg) or prednisone (5 mg/Kg), an anti-inflammatory drug. We found that oral administration of fucoidans significantly attenuated PM-induced lipid peroxidation and infiltration of inflammatory cells like F4/80+ macrophages, Gr-1+ granulocytes, and CD4+ T lymphocytes. Fucoidans also attenuated the level of PM-exacerbated IL-4, a primitive cytokine released in Th2 mediated eosinophilic asthma. This further suppressed mast cell activation, degranulation and IgE synthesis of PM exposed mice. Interestingly, fucoidans attenuated PM-exacerbated mucus hypersecretion and goblet cell hyperplasia. Therefore, our results suggest that fucoidans are effective at alleviating PM-exacerbated allergic asthma symptoms by attenuating the airway inflammatory response and mucus hypersecretion.

scholarly journals Unmet need in severe, uncontrolled asthma: can anti-TSLP therapy with tezepelumab provide a valuable new treatment option?

2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Andrew Menzies-Gow ◽  
Michael E. Wechsler ◽  
Chris E. Brightling
Keyword(s):  
Inflammatory Response ◽  
Airway Inflammation ◽  
Asthma Control ◽  
Severe Asthma ◽  
Human Monoclonal Antibody ◽  
Unmet Need ◽  
Blood Eosinophil ◽  
Biologic Therapies ◽  
Uncontrolled Asthma ◽  
Asthma Exacerbations

Abstract Despite treatment with standard-of-care medications, including currently available biologic therapies, many patients with severe asthma have uncontrolled disease, which is associated with a high risk of hospitalization and high healthcare costs. Biologic therapies approved for severe asthma have indications limited to patients with either eosinophilic or allergic phenotypes; there are currently no approved biologics for patients with eosinophil-low asthma. Furthermore, existing biologic treatments decrease exacerbation rates by approximately 50% only, which may be because they target individual, downstream elements of the asthma inflammatory response, leaving other components untreated. Targeting an upstream mediator of the inflammatory response may have a broader effect on airway inflammation and provide more effective asthma control. One such potential target is thymic stromal lymphopoietin (TSLP), an epithelial-derived cytokine released in response to multiple triggers associated with asthma exacerbations, such as viruses, allergens, pollutants and other airborne irritants. Mechanistic studies indicate that TSLP drives eosinophilic (including allergic) inflammation, neutrophilic inflammation and structural changes to the airway in asthma through actions on a wide variety of adaptive and innate immune cells and structural cells. Tezepelumab is a first-in-class human monoclonal antibody that blocks the activity of TSLP. In the phase 2b PATHWAY study (NCT02054130), tezepelumab reduced asthma exacerbations by up to 71% compared with placebo in patients with severe, uncontrolled asthma across the spectrum of inflammatory phenotypes, and improved lung function and asthma control. Phase 3 trials of tezepelumab are underway. NAVIGATOR (NCT03347279), a pivotal exacerbation study, aims to assess the potential efficacy of tezepelumab further in patients with a broad range of severe asthma phenotypes, including those with low blood eosinophil counts. SOURCE (NCT03406078) aims to evaluate the oral corticosteroid-sparing potential of tezepelumab. DESTINATION (NCT03706079) is a long-term extension study. In addition, an ongoing phase 2 bronchoscopy study, CASCADE (NCT03688074), aims to evaluate the effect of tezepelumab on airway inflammation and airway remodelling in patients across the spectrum of type 2 airway inflammation. Here, we summarize the unmet therapeutic need in severe asthma and the current treatment landscape, discuss the rationale for targeting TSLP in severe asthma therapy and describe the current development status of tezepelumab.

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