Double-stranded RNA evokes exacerbation in a mouse model of corticosteroid refractory asthma

2015 ◽  
Vol 129 (11) ◽  
pp. 973-987 ◽  
Author(s):  
Jorge De Alba ◽  
Raquel Otal ◽  
Elena Calama ◽  
Anna Domenech ◽  
Neus Prats ◽  
...  
Keyword(s):  
Mouse Model ◽  
Asthma Exacerbation ◽  
Airway Hyperreactivity ◽  
Asthma Phenotype ◽  
Double Stranded Rna ◽  
Cytokines And Chemokines ◽  
Set Up ◽  
Refractory Asthma ◽  
Viral Exacerbation ◽  
Pro Inflammatory Cytokines

We have set up a new murine model mimicking aspects of viral exacerbation in a corticosteroid-refractory asthma phenotype. Our model shows an exacerbation of airway hyperreactivity, enhanced inflammation and elevated pro-inflammatory cytokines and chemokines associated with human asthma exacerbation.

scholarly journals Mild Attenuation of the Pulmonary Inflammatory Response in a Mouse Model of Hereditary Hemochromatosis Type 4

2021 ◽  
Vol 11 ◽  
Author(s):  
Oriana Marques ◽  
Joana Neves ◽  
Natalie K. Horvat ◽  
Sandro Altamura ◽  
Martina U. Muckenthaler
Keyword(s):  
Inflammatory Response ◽  
Mouse Model ◽  
Iron Homeostasis ◽  
Pulmonary Inflammation ◽  
Hereditary Hemochromatosis ◽  
Cytokines And Chemokines ◽  
Cytokine Levels ◽  
Pulmonary Inflammatory Response ◽  
Increased Susceptibility ◽  
Pro Inflammatory Cytokines

The respiratory tract is constantly exposed to pathogens that require iron for proliferation and virulence. Pulmonary iron levels are increased in several lung diseases and associated with increased susceptibility to infections. However, regulation of lung iron homeostasis and its cross talk to pulmonary immune responses are largely unexplored. Here we investigated how increased lung iron levels affect the early pulmonary inflammatory response. We induced acute local pulmonary inflammation via aerosolized LPS in a mouse model of hereditary hemochromatosis type 4 (Slc40a1C326S/C326S), which is hallmarked by systemic and pulmonary iron accumulation, specifically in alveolar macrophages. We show that Slc40a1C326S/C326S mice display a mild attenuation in the LPS-induced pulmonary inflammatory response, with a reduced upregulation of some pro-inflammatory cytokines and chemokines. Despite mildly reduced cytokine levels, there is no short-term impairment in the recruitment of neutrophils into the bronchoalveolar space. These data suggest that increased pulmonary iron levels do not strongly alter the acute inflammatory response of the lung.

scholarly journals CD206+ macrophage is an accelerator of endometriotic-like lesion via promoting angiogenesis in the endometriosis mouse model

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yosuke Ono ◽  
Osamu Yoshino ◽  
Takehiro Hiraoka ◽  
Erina Sato ◽  
Akiko Furue ◽  
...  
Keyword(s):  
Mouse Model ◽  
Diphtheria Toxin ◽  
Immunohistochemical Study ◽  
Mrna Levels ◽  
Cytokines And Chemokines ◽  
Diphtheria Toxin Receptor ◽  
Endothelial Cell Marker ◽  
Toxin Receptor ◽  
Group A

AbstractIn endometriosis, M2 MΦs are dominant in endometriotic lesions, but the actual role of M2 MΦ is unclear. CD206 positive (+) MΦ is classified in one of M2 type MΦs and are known to produce cytokines and chemokines. In the present study, we used CD206 diphtheria toxin receptor mice, which enable to deplete CD206+ cells with diphtheria toxin (DT) in an endometriosis mouse model. The depletion of CD206+ MΦ decreased the total weight of endometriotic-like lesions significantly (p < 0.05). In the endometriotic-like lesions in the DT group, a lower proliferation of endometriotic cells and the decrease of angiogenesis were observed. In the lesions, the mRNA levels of VEGFA and TGFβ1, angiogenic factors, in the DT group significantly decreased to approximately 50% and 30% of control, respectively. Immunohistochemical study revealed the expressions of VEGFA and an endothelial cell marker CD31 in lesions of the DT group, were dim compared to those in control. Also, the number of TGFβ1 expressing MΦ was significantly reduced compared to control. These data suggest that CD206+ MΦ promotes the formation of endometriotic-like lesions by inducing angiogenesis around the lesions.

The mixture of siRNAs targeted to IL-4 and IL-13 genes effectively reduces the airway hyperreactivity and allergic inflammation in a mouse model of asthma

2022 ◽  
Vol 103 ◽  
pp. 108432
Author(s):  
Shilovskiy IP ◽  
Sundukova MS ◽  
Korneev AV ◽  
Nikolskii AA ◽  
Barvinskaya ED ◽  
...  
Keyword(s):  
Mouse Model ◽  
Allergic Inflammation ◽  
Airway Hyperreactivity

scholarly journals Smooth muscle brain‐derived neurotrophic factor contributes to airway hyperreactivity in a mouse model of allergic asthma

2018 ◽  
Vol 33 (2) ◽  
pp. 3024-3034 ◽  
Author(s):  
Rodney D. Britt ◽  
Michael A. Thompson ◽  
Sarah A. Wicher ◽  
Logan J. Manlove ◽  
Anne Roesler ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Mouse Model ◽  
Allergic Asthma ◽  
Neurotrophic Factor ◽  
Brain Derived Neurotrophic Factor ◽  
Airway Hyperreactivity

scholarly journals Associations between HBD3 and Pro-Inflammatory Cytokines in Asymptomatic Irreversible Pulpitis

2017 ◽  
pp. 14-19
Author(s):  
Anita Aminoshariae ◽  
Mohammed Bakkar ◽  
Tracey Bonfield ◽  
Santosh Ghosh ◽  
Thomas A Montagnese ◽  
...  
Keyword(s):  
Inflammatory Cytokines ◽  
Normal Group ◽  
Control Group ◽  
Spearman Correlation ◽  
Whitney Test ◽  
Cytokines And Chemokines ◽  
Luminex Technology ◽  
Spearman Correlation Test ◽  
Irreversible Pulpitis ◽  
Pro Inflammatory Cytokines

Objective: The aim of this study was to investigate the levels of Human Beta Defensin (hBD) 2 and 3, chemokine and cytokine expressions between teeth endodontically diagnosed with symptomatic irreversible pulpitis (SIP), asymptomatic irreversible pulpitis (ASIP) and normal pulps. We hypothesized that there would be a correlation between hBD’s and the immunoregulatory response. Design: Pulpal samples were collected with paper points. Six samples were obtained from normal teeth, 21 from SIP, 18 from ASIP. Levels of cytokines and betadefensins were measured by Luminex technology and ELISA, respectively. Data were statistically analyzed using Kruskal-Wallis, Wilcoxon Mann-Whitney test and Spearman correlation test. Differences were considered significant at p<0.05. Results: hBD-2 levels correlated with samples obtained from patients in the ASIP group, but not in the samples obtained from patients with SIP or the control group. HBD-3 concentrations associated with all of the cytokines and chemokines in both SIP and ASIP groups. However, in the normal group, hBD-3 correlated with only TNFα, IL-8, MCP-1, IL-1β, MIP-1a, RANTES, IL-17 in normal group. When comparing control levels of hBD-2 and hBD-3 with patients samples from either the ASIP or the SIP groups, hBD-2 and hBD-3 concentrations were highest in the ASIP group. Conclusions: The hBD-2 and-3 were highly associated with the levels of the chemokines and cytokines in ASIP group. HBD-3 concentrations correlate with the levels of the chemokines and the cytokines in the SIP and ASIP groups.

Blocking ATP releasing channels prevents high extracellular ATP levels and airway hyperreactivity in an asthmatic mouse model

2021 ◽  
Author(s):  
Llilian Arzola Martínez ◽  
Rebeca Benavente ◽  
Génesis Vega ◽  
Mariana Ríos ◽  
Wendy Fonseca ◽  
...  
Keyword(s):  
Mouse Model ◽  
Airway Inflammation ◽  
Airway Epithelium ◽  
Atp Release ◽  
Specific Inhibitor ◽  
Extracellular Atp ◽  
Airway Hyperreactivity ◽  
Luciferase Assay ◽  
Asthmatic Patients ◽  
Allergic Mouse

Allergic asthma is a chronic airway inflammatory response to different triggers like inhaled allergens. Excessive ATP in fluids from asthmatic patients is considered an inflammatory signal and an important autocrine/paracrine modulator of airway physiology. Here we investigated the deleterious effect of increased extracellular ATP (eATP) concentration on the mucociliary clearance (MCC) effectiveness and determined the role of ATP releasing channels during airway inflammation in an ovalbumin (OVA)-sensitized mouse model. Our allergic mouse model exhibited high levels of eATP measured in the tracheal fluid with a luciferin-luciferase assay and reduced MCC velocity determined by microspheres tracking in the trachea ex vivo. Addition of ATP had a dual effect on MCC, where lower ATP concentration (µM) increased microspheres velocity, while higher concentration (mM) transiently stopped microspheres movement. Also, an augmented ethidium bromide uptake by the allergic tracheal airway epithelium suggests an increase in ATP release channel functionality during inflammatory conditions. The use of carbenoxolone, a non-specific inhibitor of connexin and pannexin1channels reduced the eATP concentration in the allergic mouse tracheal fluid and dye uptake by the airway epithelium, providing evidence that these ATP release channels are facilitating the net flux of ATP to the lumen during airway inflammation. However, only the specific inhibition of pannexin1 with 10Panx peptide significantly reduced eATP in bronchoalveolar lavage and decreased airway hyperresponsiveness in OVA-allergic mouse model. These data provide evidence that blocking eATP may be a pharmacological alternative to be explored in rescue therapy during episodes of airflow restriction in asthmatic patients.

scholarly journals Mild electrical stimulation with heat shock attenuates renal pathology in adriamycin-induced nephrotic syndrome mouse model

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Keisuke Teramoto ◽  
Yu Tsurekawa ◽  
Mary Ann Suico ◽  
Shota Kaseda ◽  
Kohei Omachi ◽  
...  
Keyword(s):  
Nephrotic Syndrome ◽  
Electrical Stimulation ◽  
Heat Shock ◽  
Mouse Model ◽  
Akt Inhibitor ◽  
First Line ◽  
Renal Disorder ◽  
Apoptotic Effect ◽  
Pro Inflammatory Cytokines

Abstract Nephrotic syndrome (NS) is a renal disorder that is characterized by massive proteinuria, hypoalbuminemia and edema. One of the main causes of NS is focal segmental glomerulosclerosis (FSGS), which has extremely poor prognosis. Although steroids and immunosuppressants are the first line of treatment, some FSGS cases are refractory, prompting the need to find new therapeutic strategies. We have previously demonstrated that an optimized combination treatment of mild electrical stimulation (MES) and heat shock (HS) has several biological benefits including the amelioration of the pathologies of the genetic renal disorder Alport syndrome. Here, we investigated the effect of MES + HS on adriamycin (ADR)-induced NS mouse model. MES + HS suppressed proteinuria and glomerulosclerosis induced by ADR. The expressions of pro-inflammatory cytokines and pro-fibrotic genes were also significantly downregulated by MES + HS. MES + HS decreased the expression level of cleaved caspase-3 and the number of TUNEL-positive cells, indicating that MES + HS exerted anti-apoptotic effect. Moreover, MES + HS activated the Akt signaling and induced the phosphorylation and inhibition of the apoptotic molecule BAD. In in vitro experiment, the Akt inhibitor abolished the MES + HS-induced Akt-BAD signaling and anti-apoptotic effect in ADR-treated cells. Collectively, our study suggested that MES + HS modulates ADR-induced pathologies and has renoprotective effect against ADR-induced NS via regulation of Akt-BAD axis.

Inhaled Carbenoxolone Prevents Allergic Airway Inflammation and Airway Hyperreactivity in a Mouse Model of Asthma

2008 ◽  
Vol 149 (1) ◽  
pp. 38-46 ◽  
Author(s):  
Arjun Ram ◽  
Shashi Kant Singh ◽  
Vijay Pal Singh ◽  
Sarvesh Kumar ◽  
Balaram Ghosh
Keyword(s):  
Mouse Model ◽  
Airway Inflammation ◽  
Allergic Airway Inflammation ◽  
Airway Hyperreactivity

Development of a mouse model mimicking key aspects of a viral asthma exacerbation

2013 ◽  
Vol 126 (8) ◽  
pp. 567-580 ◽  
Author(s):  
Deborah L. Clarke ◽  
Nicola H. E. Davis ◽  
Jayesh B. Majithiya ◽  
Sian C. Piper ◽  
Arthur Lewis ◽  
...  
Keyword(s):  
Mouse Model ◽  
Asthma Exacerbation ◽  
Resistant Mouse ◽  
Disease Mechanisms ◽  
Asthma Exacerbations ◽  
Key Aspects ◽  
Novel Therapeutic

The present study describes a corticosteroid-resistant mouse model mimicking key aspects of viral asthma exacerbation which may provide better understanding of disease mechanisms and could be used to build early confidence in novel therapeutic axes targeting viral asthma exacerbations in asthmatics.

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