scholarly journals Depletion of microRNA-451 in response to allergen exposure accentuates asthmatic inflammation by regulating Sirtuin2

2020 ◽  
Vol 318 (5) ◽  
pp. L921-L930
Author(s):  
Sangwoon Chung ◽  
Yong Gyu Lee ◽  
Manjula Karpurapu ◽  
Joshua A. Englert ◽  
Megan N. Ballinger ◽  
...  
Keyword(s):  
Gene Expression ◽  
Airway Inflammation ◽  
Macrophage Activation ◽  
Airway Remodeling ◽  
Oxidant Stress ◽  
Allergic Inflammation ◽  
Allergic Airway Inflammation ◽  
Health Concern ◽  
Macrophage Phenotype

The incidence of asthma has increased from 5.5% to near 8% of the population, which is a major health concern. The hallmarks of asthma include eosinophilic airway inflammation that is associated with chronic airway remodeling. Allergic airway inflammation is characterized by a complex interplay of resident and inflammatory cells. MicroRNAs (miRNAs) are small noncoding RNAs that function as posttranscriptional modulators of gene expression. However, the role of miRNAs, specifically miR-451, in the regulation of allergic airway inflammation is unexplored. Our previous findings showed that oxidant stress regulates miR-451 gene expression in macrophages during an inflammatory process. In this paper, we examined the role of miR-451 in regulating macrophage phenotype using an experimental poly-allergenic murine model of allergic airway inflammation. We found that miR-451 contributes to the allergic induction of CCL17 in the lung and plays a key role in proasthmatic macrophage activation. Remarkably, administration of a Sirtuin 2 (Sirt2) inhibitor diminished alternate macrophage activation and markedly abrogated triple-allergen [dust mite, ragweed, Aspergillus fumigatus (DRA)]-induced lung inflammation. These data demonstrate a role for miR-451 in modulating allergic inflammation by influencing allergen-mediated macrophages phenotype.

scholarly journals HDAC2 attenuates airway inflammation by suppressing IL-17A production in HDM-challenged mice

2019 ◽  
Vol 316 (1) ◽  
pp. L269-L279 ◽  
Author(s):  
Tianwen Lai ◽  
Mindan Wu ◽  
Chao Zhang ◽  
Luanqing Che ◽  
Feng Xu ◽  
...  
Keyword(s):  
Airway Inflammation ◽  
Inflammatory Cytokines ◽  
Allergic Inflammation ◽  
Allergic Airway Inflammation ◽  
Inflammatory Cells ◽  
Protective Role ◽  
In Vivo Models

Histone deacetylase (HDAC)2 is expressed in airway epithelium and plays a pivotal role in inflammatory cells. However, the role of HDAC2 in allergic airway inflammation remains poorly understood. In the present study, we determined the role of HDAC2 in airway inflammation using in vivo models of house dust mite (HDM)-induced allergic inflammation and in vitro cultures of human bronchial epithelial (HBE) cells exposed to HDM, IL-17A, or both. We observed that HDM-challenged Hdac2+/− mice exhibited substantially enhanced infiltration of inflammatory cells. Higher levels of T helper 2 cytokines and IL-17A expression were found in lung tissues of HDM-challenged Hdac2+/− mice. Interestingly, IL-17A deletion or anti-IL-17A treatment reversed the enhanced airway inflammation induced by HDAC2 impairment. In vitro, HDM and IL-17A synergistically decreased HDAC2 expression in HBE cells. HDAC2 gene silencing further enhanced HDM- and/or IL-17A-induced inflammatory cytokines in HBE cells. HDAC2 overexpresion or blocking IL-17A gene expression restored the enhanced inflammatory cytokines. Collectively, these results support a protective role of HDAC2 in HDM-induced airway inflammation by suppressing IL-17A production and might suggest that activation of HDAC2 and/or inhibition of IL-17A production could prevent the development of allergic airway inflammation.

scholarly journals CCR9 Is a Key Regulator of Early Phases of Allergic Airway Inflammation

2016 ◽  
Vol 2016 ◽  
pp. 1-16 ◽  
Author(s):  
C. López-Pacheco ◽  
G. Soldevila ◽  
G. Du Pont ◽  
R. Hernández-Pando ◽  
E. A. García-Zepeda
Keyword(s):  
Airway Inflammation ◽  
Chemokine Receptors ◽  
Allergic Inflammation ◽  
Allergic Airway Inflammation ◽  
Cell Recruitment ◽  
Inflammatory Cell Recruitment ◽  
First Time ◽  
Early Phases ◽  
Deficient Mice

Airway inflammation is the most common hallmark of allergic asthma. Chemokine receptors involved in leukocyte recruitment are closely related to the pathology in asthma. CCR9 has been described as a homeostatic and inflammatory chemokine receptor, but its role and that of its ligand CCL25 during lung inflammation remain unknown. To investigate the role of CCR9 as a modulator of airway inflammation, we established an OVA-induced allergic inflammation model in CCR9-deficient mice. Here, we report the expression of CCR9 and CCL25 as early as 6 hours post-OVA challenge in eosinophils and T-lymphocytes. Moreover, in challenged CCR9-deficient mice, cell recruitment was impaired at peribronchial and perivenular levels. OVA-administration in CCR9-deficient mice leads to a less inflammatory cell recruitment, which modifies the expression of IL-10, CCL11, and CCL25 at 24 hours after OVA challenge. In contrast, the secretion of IL-4 and IL-5 was not affected in CCR9-deficient mice compared to WT mice. These results demonstrate for the first time that CCR9 and CCL25 expressions are induced in the early stages of airway inflammation and they have an important role modulating eosinophils and lymphocytes recruitment at the first stages of inflammatory process, suggesting that they might be a potential target to regulate inflammation in asthma.

scholarly journals High molecular weight hyaluronan ameliorates allergic inflammation and airway hyperresponsiveness in the mouse

2018 ◽  
Vol 315 (5) ◽  
pp. L787-L798 ◽  
Author(s):  
Collin G. Johnson ◽  
Vandy P. Stober ◽  
Jaime M. Cyphert-Daly ◽  
Carol S. Trempus ◽  
Gordon P. Flake ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Airway Inflammation ◽  
High Molecular Weight ◽  
Airway Hyperresponsiveness ◽  
Allergic Sensitization ◽  
Coiled Coil ◽  
Allergic Inflammation ◽  
Allergic Airway Inflammation ◽  
Heavy Chains

Allergic asthma is a major cause of morbidity in both pediatric and adult patients. Recent research has highlighted the role of hyaluronan (HA), an extracellular matrix glycosaminoglycan, in asthma pathogenesis. Experimental allergic airway inflammation and clinical asthma are associated with an increase of shorter fragments of HA (sHA), which complex with inter-α-inhibitor heavy chains (HCs) and induce inflammation and airway hyperresponsiveness (AHR). Importantly, the effects of sHA can be antagonized by the physiological counterpart high molecular weight HA (HMWHA). We used a mouse model of house dust mite-induced allergic airway inflammation and demonstrated that instilled HMWHA ameliorated allergic airway inflammation and AHR, even when given after the establishment of allergic sensitization and after challenge exposures. Furthermore, instilled HMWHA reduced the development of HA-HC complexes and the activation of Rho-associated, coiled-coil containing protein kinase 2. We conclude that airway application of HMWHA is a potential treatment for allergic airway inflammation.

scholarly journals O21 - The role of DNA damage and repair in allergic airway inflammation

2014 ◽  
Vol 4 (Suppl 1) ◽  
pp. O21
Author(s):  
Tze Khee Chan ◽  
Xin Yi Loh ◽  
Daniel WS Tan ◽  
Bevin P Engelward ◽  
Fred WS Wong
Keyword(s):  
Dna Damage ◽  
Airway Inflammation ◽  
Allergic Airway Inflammation ◽  
Dna Damage And Repair

Exhaled nitric oxide estimation by a simple and efficient noninvasive technique and its utility as a marker of airway inflammation in mice

2009 ◽  
Vol 107 (1) ◽  
pp. 295-301 ◽  
Author(s):  
Tanveer Ahmad ◽  
Ulaganathan Mabalirajan ◽  
Duraisamy Arul Joseph ◽  
Lokesh Makhija ◽  
Vijay Pal Singh ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Airway Inflammation ◽  
Airway Remodeling ◽  
Allergen Challenge ◽  
Allergic Airway Inflammation ◽  
Ambient Air ◽  
Exhaled Nitric Oxide ◽  
Noninvasive Technique ◽  
Modified Method ◽  
Chronic Models

Allergic airway inflammation (AI) is commonly associated with enhanced exhaled nitric oxide (ENO) in both humans and mice. Since mouse models are being used to understand various mechanisms of asthma, a noninvasive, simple, and reproducible method to determine ENO in mice is required for serial nonterminal assessment that can be used independent of environmental situations in which the ambient air contains substantial amounts of NO as a contaminant. The aim of this study was to noninvasively measure ENO in individual mice and to test its utility as a marker of AI in different models of allergic AI. We modified the existing ENO measuring methods by incorporating flushing and washout steps that allowed simple but reliable measurements under highly variable ambient NO conditions (1–100 ppb). This method was used to serially follow ENO in acute and chronic models of allergic AI in mice. ENO was reproducibly measured by this modified method and was positively correlated to AI in both acute and chronic models of asthma but was not independently related to airway remodeling. Resolution of AI and other related parameters in dexamethasone-treated mice resulted in reduction of ENO, further confirming this association. Restriction of allergen challenge to pulmonary but not nasal airways was associated with a smaller increase in ENO compared with allergen challenge to both. Hence, ENO can now be reliably measured in mice independent of ambient NO levels and is a valid biomarker for AI. However, nasal and pulmonary airways are likely to be independent sources of ENO, and any results must be interpreted as such.

scholarly journals Multi-Faceted Notch in Allergic Airway Inflammation

2019 ◽  
Vol 20 (14) ◽  
pp. 3508
Author(s):  
Miao-Tzu Huang ◽  
Chiao-Juno Chiu ◽  
Bor-Luen Chiang
Keyword(s):  
Embryonic Development ◽  
Notch Signaling ◽  
Airway Inflammation ◽  
Cell Activity ◽  
Adult Life ◽  
Allergic Airway Inflammation ◽  
T Cell Subsets ◽  
Cell Fate Decisions ◽  
Physiological Processes

Notch is an evolutionarily conserved signaling family which iteratively exerts pleiotropic functions in cell fate decisions and various physiological processes, not only during embryonic development but also throughout adult life. In the context of the respiratory system, Notch has been shown to regulate ciliated versus secretory lineage differentiation of epithelial progenitor cells and coordinate morphogenesis of the developing lung. Reminiscent of its role in development, the Notch signaling pathway also plays a role in repair of lung injuries by regulation of stem cell activity, cell differentiation, cell proliferation and apoptosis. In addition to functions in embryonic development, cell and tissue renewal and various physiological processes, including glucose and lipid metabolism, Notch signaling has been demonstrated to regulate differentiation of literally almost all T-cell subsets, and impact on elicitation of inflammatory response and its outcome. We have investigated the role of Notch in allergic airway inflammation in both acute and chronic settings. In this mini-review, we will summarize our own work and recent advances on the role of Notch signaling in allergic airway inflammation, and discuss potential applications of the Notch signaling family in therapy for allergic airway diseases.

scholarly journals Role of Interleukin-25 in allergic airway inflammation and vascular damage

2011 ◽  
Vol 31 (5) ◽  
pp. 420-424
Author(s):  
Hiroshi Nakajima ◽  
Saki Kawashima ◽  
Tomohiro Tamachi ◽  
Kentaro Takahashi ◽  
Koichi Hirose
Keyword(s):  
Airway Inflammation ◽  
Allergic Airway Inflammation ◽  
Vascular Damage ◽  
Interleukin 25

scholarly journals Exacerbation of Allergic Airway Inflammation in Mice Lacking ECTO-5′-Nucleotidase (CD73)

2020 ◽  
Vol 11 ◽  
Author(s):  
Elisabetta Caiazzo ◽  
Ida Cerqua ◽  
Maria Antonietta Riemma ◽  
Roberta Turiello ◽  
Armando Ialenti ◽  
...  
Keyword(s):  
Airway Inflammation ◽  
Allergic Sensitization ◽  
Adaptive Immune Response ◽  
Allergic Airway Inflammation ◽  
Individual Response ◽  
Type I ◽  
Target Tissue ◽  
Extracellular Adenosine ◽  
Reduced Frequency

The airways are a target tissue of type I allergies and atopy is the main etiological factor of bronchial asthma. A predisposition to allergy and individual response to allergens are dependent upon environmental and host factors. Early studies performed to clarify the role of extracellular adenosine in the airways highlighted the importance of adenosine-generating enzymes CD73, together with CD39, as an innate protection system against lung injury. In experimental animals, deletion of CD73 has been associated with immune and autoimmune diseases. Our experiments have been performed to investigate the role of CD73 in the assessment of allergic airway inflammation following sensitization. We found that in CD73−/− mice sensitization, induced by subcutaneous ovalbumin (OVA) administration, increased signs of airway inflammation and atopy developed, characterized by high IgE plasma levels and increased pulmonary cytokines, reduced frequency of lung CD4+CD25+Foxp3+ T cells, but without bronchial hyperreactivity, compared to sensitized wild type mice. Our results provide evidence that the lack of CD73 causes an uncontrolled allergic sensitization, suggesting that CD73 is a key molecule at the interface between innate and adaptive immune response. The knowledge of host immune factors controlling allergic sensitization is of crucial importance and might help to find preventive interventions that could act before an allergy develops.

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