scholarly journals Corticosteroid Insensitivity Persists in the Absence of STAT1 Signaling in Severe Allergic Airway Inflammation

2021 ◽  
Author(s):  
Brandon W. Lewis ◽  
Devine Jackson ◽  
Stephanie A Amici ◽  
Joshua Walum ◽  
Manel Guessas ◽  
...  
Keyword(s):  
Airway Inflammation ◽  
Severe Asthma ◽  
Mucous Cell ◽  
Airflow Obstruction ◽  
Allergic Airway Inflammation ◽  
Corticosteroid Treatment ◽  
Cell Infiltration ◽  
Eosinophil Infiltration ◽  
Th1 Cell ◽  
Airway Pathology

Corticosteroid insensitivity in asthma limits the ability to effectively manage severe asthma, which is characterized by persistent airway inflammation, airway hyperresponsiveness (AHR), and airflow obstruction despite corticosteroid treatment. Recent reports indicate that corticosteroid insensitivity is associated with increased interferon-gamma (IFN-g) levels and T-helper (Th) 1 lymphocyte infiltration in severe asthma. Signal Transducer and Activator of Transcription 1 (STAT1) activation by IFN-g is a key signaling pathway in Th1 inflammation, however its role in the context of severe allergic airway inflammation and corticosteroid sensitivity remains unclear. In the present study, we challenged wild type (WT) and Stat1-/- mice with mixed allergens (MA) augmented with c-di-GMP, an inducer of Th1 cell infiltration with increased eosinophils, neutrophils, Th1, Th2, and Th17 cells. Compared to WT mice, Stat1-/- had reduced neutrophils, Th1 and Th17 cell infiltration. To evaluate corticosteroid sensitivity, mice were treated with either vehicle, 1 or 3 mg/kg fluticasone propionate (FP). Corticosteroid significantly reduced eosinophil infiltration and cytokine levels in both c-di-GMP + MA-challenged WT and Stat1-/- mice. However, histological and functional analyses show that corticosteroids did not reduce airway inflammation, epithelial mucous cell abundance, airway smooth muscle mass, and AHR in c-di-GMP + MA-challenged WT or Stat1-/- mice. Collectively, our data suggest that increased Th1 inflammation is associated with a decrease in corticosteroid sensitivity. However, increased airway pathology and AHR persist in the absence of STAT1 indicate corticosteroid insensitivity in structural airway cells is a STAT1 independent process.

scholarly journals Low-Dose Intestinal Trichuris muris Infection Alters the Lung Immune Microenvironment and Can Suppress Allergic Airway Inflammation

2015 ◽  
Vol 84 (2) ◽  
pp. 491-501 ◽  
Author(s):  
Alistair L. Chenery ◽  
Frann Antignano ◽  
Kyle Burrows ◽  
Sebastian Scheer ◽  
Georgia Perona-Wright ◽  
...  
Keyword(s):  
Airway Inflammation ◽  
Cross Talk ◽  
Low Dose ◽  
Intestinal Inflammation ◽  
Allergic Airway Inflammation ◽  
Interleukin 10 ◽  
Th1 Cell ◽  
Trichuris Muris ◽  
Airway Pathology

Immunological cross talk between mucosal tissues such as the intestine and the lung is poorly defined during homeostasis and disease. Here, we show that a low-dose infection with the intestinally restricted helminth parasiteTrichuris murisresults in the production of Th1 cell-dependent gamma interferon (IFN-γ) and myeloid cell-derived interleukin-10 (IL-10) in the lung without causing overt airway pathology. This cross-mucosal immune response in the lung inhibits the development of papain-induced allergic airway inflammation, an innate cell-mediated type 2 airway inflammatory disease. Thus, we identify convergent and nonredundant roles of adaptive and innate immunity in mediating cross-mucosal suppression of type 2 airway inflammation during low-dose helminth-induced intestinal inflammation. These results provide further insight in identifying novel intersecting immune pathways elicited by gut-to-lung mucosal cross talk.

scholarly journals Diabetes Downregulates Allergen-Induced Airway Inflammation in Mice

2018 ◽  
Vol 2018 ◽  
pp. 1-11 ◽  
Author(s):  
Vinicius F. Carvalho ◽  
Emiliano O. Barreto ◽  
Ana Carolina S. Arantes ◽  
Magda F. Serra ◽  
Tatiana Paula T. Ferreira ◽  
...  
Keyword(s):  
Airway Inflammation ◽  
Bronchoalveolar Lavage Fluid ◽  
Allergic Airway Inflammation ◽  
Allergic Diseases ◽  
Lavage Fluid ◽  
Airway Hyperreactivity ◽  
Eosinophil Infiltration ◽  
Mucus Production ◽  
Diabetes Induction

Previous studies described that allergic diseases, including asthma, occur less often than expected in patients with type 1 diabetes. Here, we investigated the influence of diabetes on allergic airway inflammation in a model of experimental asthma in mice. Diabetes was induced by intravenous injection of alloxan into 12 h-fasted A/J mice, followed by subcutaneous sensitization with ovalbumin (OVA) and aluminum hydroxide (Al(OH)3), on days 5 and 19 after diabetes induction. Animals were intranasally challenged with OVA (25 μg), from day 24 to day 26. Alloxan-induced diabetes significantly attenuated airway inflammation as attested by the lower number of total leukocytes in the bronchoalveolar lavage fluid, mainly neutrophils and eosinophils. Suppression of eosinophil infiltration in the peribronchiolar space and generation of eosinophilotactic mediators, such as CCL-11/eotaxin, CCL-3/MIP-1α, and IL-5, were noted in the lungs of diabetic sensitized mice. In parallel, reduction of airway hyperreactivity (AHR) to methacholine, mucus production, and serum IgE levels was also noted under diabetic conditions. Our findings show that alloxan diabetes caused attenuation of lung allergic inflammatory response in A/J mice, by a mechanism possibly associated with downregulation of IgE antibody production.

scholarly journals Changes in Pulmonary Function and Parasite Burden in Rats Infected with Strongyloides venezuelensis Concomitant with Induction of Allergic Airway Inflammation

2003 ◽  
Vol 71 (5) ◽  
pp. 2607-2614 ◽  
Author(s):  
Deborah Negrão-Corrêa ◽  
Micheline R. Silveira ◽  
Cynthia M. Borges ◽  
Danielle G. Souza ◽  
Mauro M. Teixeira
Keyword(s):  
Airway Inflammation ◽  
Mutual Influence ◽  
Pulmonary Inflammation ◽  
Allergic Airway Inflammation ◽  
Parasite Burden ◽  
Allergic Diseases ◽  
Lavage Fluid ◽  
Eosinophil Infiltration ◽  
Asthmatic Patients ◽  
Strongyloides Venezuelensis

ABSTRACT The prevalence of allergic diseases such as asthma has increased markedly over the past few decades. To evaluate the possible mutual influence of helminth infection and allergy, the combined effects of experimental allergic airway inflammation and infection with Strongyloides venezuelensis on various parasitological and inflammatory indices were evaluated in the rat. A challenge of immunized rats with aerosolized ovalbumin (OVA) resulted in eosinophilic inflammation that peaked 48 h after the challenge and was accompanied by airway hyperresponsiveness (AHR) to an intravenous acetylcholine challenge. S. venezuelensis infection concomitant with an OVA challenge of immunized rats resulted in prolonged pulmonary inflammation with increased eosinophil infiltration in bronchoalveolar lavage fluid but not in the lung tissue. These rats also showed a significant parasite burden reduction, especially during parasite migration through the lungs. However, the fecundity rates of worms that reached the intestine were similar in allergic and nonallergic animals. Despite airway inflammation, the increased responsiveness of the airways in the experimental asthma model was suppressed during parasite migration through the lungs (2 days). In contrast, parasite-induced AHR was unchanged 5 days after infection in immunized and challenged rats. In conclusion, infection with S. venezuelensis interfered with the onset of AHR following an antigen challenge of immunized rats. The ability of parasites to switch off functional airway responses is therapeutically relevant because we may learn from parasites how to modulate lung function and, hence, the AHR characteristic of asthmatic patients.

scholarly journals A Selective α7 Nicotinic Acetylcholine Receptor Agonist, PNU-282987, Attenuates ILC2s Activation and Alternaria-Induced Airway Inflammation

2021 ◽  
Vol 11 ◽  
Author(s):  
Fang Yuan ◽  
Lili Jiang ◽  
Qianyang Li ◽  
Leon Sokulsky ◽  
Yuanyuan Wanyan ◽  
...  
Keyword(s):  
Airway Inflammation ◽  
Allergic Airway Inflammation ◽  
Treated Group ◽  
Lymphoid Cells ◽  
Eosinophil Infiltration ◽  
Α7 Nicotinic Acetylcholine Receptor ◽  
Cell Hyperplasia ◽  
Isolated Lung ◽  
Airway Eosinophil Infiltration

BackgroundThe anti-inflammatory effect of an α7nAChR agonist, PNU-282987, has previously been explored in the context of inflammatory disease. However, the effects of PNU-282987 on type 2 innate lymphoid cells (ILC2s)-mediated allergic airway inflammation has not yet been established.AimsTo determine the effects of PNU-282987 on the function of ILC2s in the context of IL-33– or Alternaria Alternata (AA)– induced airway inflammation.MethodsPNU-282987 was administered to mice that received recombinant IL-33 or AA intranasal challenges. Lung histological analysis and flow cytometry were performed to determine airway inflammation and the infiltration and activation of ILC2s. The previously published α7nAChR agonist GTS-21 was employed as a comparable reagent. ILC2s were isolated from murine lung tissue and cultured in vitro in the presence of IL-33, IL-2, and IL-7 with/without either PNU-282987 or GTS-21. The expression of the transcription factors GATA3, IKK, and NF-κB were also determined.ResultsPNU-282987 and GTS-21 significantly reduced goblet cell hyperplasia in the airway, eosinophil infiltration, and ILC2s numbers in BALF, following IL-33 or AA challenge. In vitro IL-33 stimulation of isolated lung ILC2s showed a reduction of GATA3 and Ki67 in response to PNU-282987 or GTS-21 treatments. There was a significant reduction in IKK and NF-κB phosphorylation in the PNU-282987–treated group when compared to the GTS-21–treated ILC2s.ConclusionPNU-282987 inhibits ILC2-associated airway inflammation, where its effects were comparable to that of GTS-21.

Airway pathology in severe asthma is related to airflow obstruction but not symptom control

Allergy ◽  
2017 ◽  
Vol 73 (3) ◽  
pp. 635-643 ◽  
Author(s):  
D. S. Ferreira ◽  
R. M. Carvalho-Pinto ◽  
M. G. Gregório ◽  
R. Annoni ◽  
A. M. Teles ◽  
...  
Keyword(s):  
Severe Asthma ◽  
Symptom Control ◽  
Airflow Obstruction ◽  
Airway Pathology

scholarly journals The Fermented Soy Product ImmuBalanceTM Suppresses Airway Inflammation in a Murine Model of Asthma

Nutrients ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 3380
Author(s):  
Hideaki Kadotani ◽  
Kazuhisa Asai ◽  
Atsushi Miyamoto ◽  
Kohei Iwasaki ◽  
Takahiro Kawai ◽  
...  
Keyword(s):  
Bronchoalveolar Lavage ◽  
Airway Inflammation ◽  
Murine Model ◽  
Bronchoalveolar Lavage Fluid ◽  
Inflammatory Cell ◽  
Allergic Airway Inflammation ◽  
Lavage Fluid ◽  
Cell Infiltration ◽  
Mucus Production ◽  
Cell Counts

The fermented soy product ImmuBalance contains many active ingredients and its beneficial effects on some allergic diseases have been reported. We hypothesized that ImmuBalance could have potential effects on airway inflammation in a murine model of asthma. Mice sensitized and challenged with ovalbumin developed airway inflammation. Bronchoalveolar lavage fluid was assessed for inflammatory cell counts and levels of cytokines. Lung tissues were examined for cell infiltration and mucus hypersecretion. Oral administration of ImmuBalance significantly inhibited ovalbumin-induced eosinophilic inflammation and decreased Th2 cytokine levels in bronchoalveolar lavage fluid (p < 0.05). In addition, lung histological analysis showed that ImmuBalance inhibited inflammatory cell infiltration and airway mucus production. Our findings suggest that supplementation with ImmuBalance may provide a novel strategy for the prevention or treatment of allergic airway inflammation.

scholarly journals ASSOCIATION OF MUCUS PLUGS WITH AIRFLOW OBSTRUCTION AND AIRWAY INFLAMMATION IN MODERATE TO SEVERE ASTHMA

CHEST Journal ◽  
2020 ◽  
Vol 158 (4) ◽  
pp. A19
Author(s):  
Kanami Tamura ◽  
Toshihiro Shirai ◽  
Satoshi Kato ◽  
Hiromasa Nakayasu ◽  
Toshihiro Masuda ◽  
...  
Keyword(s):  
Airway Inflammation ◽  
Severe Asthma ◽  
Airflow Obstruction
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