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 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 A20-binding inhibitor of NF-κB (ABIN) 2 negatively regulates allergic airway inflammation

2018 ◽  
Vol 215 (11) ◽  
pp. 2737-2747 ◽  
Author(s):  
Sonia Ventura ◽  
Florencia Cano ◽  
Yashaswini Kannan ◽  
Felix Breyer ◽  
Michael J. Pattison ◽  
...  
Keyword(s):  
Airway Inflammation ◽  
Drug Target ◽  
Allergic Inflammation ◽  
Allergic Airway Inflammation ◽  
Negative Regulator ◽  
Disease Models ◽  
Wild Type ◽  
Dust Mite ◽  
Airway Responses ◽  
Deficient Mice

TPL-2 MAP 3-kinase promotes inflammation in numerous mouse disease models and is an attractive anti-inflammatory drug target. However, TPL-2–deficient (Map3k8−/−) mice develop exacerbated allergic airway inflammation to house dust mite (HDM) compared with wild type controls. Here, we show that Map3k8D270A/D270A mice expressing kinase dead TPL-2 had an unaltered response to HDM, indicating that the severe airway inflammation observed in Map3k8−/− mice is not due to blockade of TPL-2 signaling and rather reflects a TPL-2 adaptor function. Severe allergic inflammation in TPL-2–deficient mice was likely due to reduced levels of ABIN-2 (TNIP2), whose stability depends on TPL-2 expression. Tnip2E256K knock-in mutation, which reduced ABIN-2 binding to A20, augmented the HDM-induced airway inflammation, but did not affect TPL-2 expression or signaling. These results identify ABIN-2 as a novel negative regulator of allergic airway responses and importantly indicate that TPL-2 inhibitors would not have unwanted allergic comorbidities.

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 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 Role of IL-17 and Th17 Cells in Liver Diseases

2011 ◽  
Vol 2011 ◽  
pp. 1-12 ◽  
Author(s):  
Linda Hammerich ◽  
Felix Heymann ◽  
Frank Tacke
Keyword(s):  
Chemokine Receptors ◽  
Liver Diseases ◽  
Th17 Cells ◽  
Hepatic Inflammation ◽  
T Helper ◽  
Disease Etiology ◽  
Cell Recruitment ◽  
Cell Responses ◽  
Injured Liver

Unbalanced Th1/Th2 T-cell responses in the liver are a characteristic of hepatic inflammation and subsequent liver fibrosis. The recently discovered Th17 cells, a subtype of CD4+T-helper cells mainly producing IL-17 and IL-22, have initially been linked to host defense against infections and to autoimmunity. Their preferred differentiation upon TGFβand IL-6, two cytokines abundantly present in injured liver, makes a contribution of Th17 cells to hepatic inflammation very likely. Indeed, initial studies in humans revealed activated Th17 cells and Th17-related cytokines in various liver diseases. However, functional experiments in mouse models are not fully conclusive at present, and the pathogenic contribution of Th17 cells to liver inflammation might vary upon the disease etiology, for example, between infectious and autoimmune disorders. Understanding the chemokines and chemokine receptors promoting hepatic Th17 cell recruitment (possibly CCR6 or CCR4) might reveal new therapeutic targets interfering with Th17 migration or differentiation in liver disease.

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

scholarly journals Improved heart function follows enhanced inflammatory cell recruitment and angiogenesis in 11βHSD1-deficient mice post-MI

2010 ◽  
Vol 88 (1) ◽  
pp. 159-167 ◽  
Author(s):  
Sara J. McSweeney ◽  
Patrick W.F. Hadoke ◽  
Agnieszka M. Kozak ◽  
Gary R. Small ◽  
Hiba Khaled ◽  
...  
Keyword(s):  
Inflammatory Cell ◽  
Heart Function ◽  
Cell Recruitment ◽  
Inflammatory Cell Recruitment ◽  
Deficient Mice

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 2215

2017 ◽  
Vol 1 (S1) ◽  
pp. 3-3
Author(s):  
Timothy P. Moran ◽  
Robert M. Immormino ◽  
Hideki Nakano ◽  
David Peden ◽  
Donald N. Cook
Keyword(s):  
Flow Cytometry ◽  
Airway Inflammation ◽  
Allergic Asthma ◽  
Immune Cells ◽  
Inflammatory Responses ◽  
Ex Vivo ◽  
Allergic Airway Inflammation ◽  
Surface Protein ◽  
Fold Increase ◽  
Deficient Mice

OBJECTIVES/SPECIFIC AIMS: Allergic asthma is a chronic lung disease driven by inappropriate inflammatory responses against inhaled allergens. Neuropilin-2 (NRP2) is a pleiotropic transmembrane receptor expressed in the lung, but its role in allergic airway inflammation is unknown. Here, we characterized NRP2 expression in lung immune cells and investigated the effects of NRP2 deficiency on airway inflammation. METHODS/STUDY POPULATION: NRP2 expression by lung immune cells from NRP2 reporter mice was determined by flow cytometry. NRP2 expression by human alveolar macrophages (AM) from healthy individuals was determined by mRNA analysis and flow cytometry. Airway inflammation in NRP2-deficient mice was assessed by bronchoalveolar lavage (BAL) cytology and inflammatory gene expression in lung tissue. RESULTS/ANTICIPATED RESULTS: NRP2 expression in lung immune cells was negligible under steady-state conditions. In contrast, inhalational exposure to lipopolysaccharide (LPS) adjuvant dramatically induced NRP2 expression in AM, as 63.3% of AM from LPS-treated mice were NRP2+ compared with 1.5% of AM from control mice. Ex vivo treatment of human AM with LPS resulted in a 1.5-fold and 2.6-fold increase in NRP2 mRNA and surface protein expression, respectively. Compared to littermate controls, NRP2-deficient mice had greater numbers of BAL leukocytes and increased lung expression of the T helper type 2 cytokines IL-4 and IL-5. Furthermore, NRP2 deficiency resulted in stochastic development of allergic airway inflammation, as spontaneous airway eosinophilia was detected in 25% (2/8) of NRP2-deficient mice compared with 0% (0/8) of littermate controls. DISCUSSION/SIGNIFICANCE OF IMPACT: NRP2 is expressed by activated human and murine AM and suppresses the spontaneous development of allergic airway inflammation. These findings suggest that NRP2 may play a key role in allergic asthma pathogenesis, and could prove to be an important therapeutic target in patients with asthma and other allergic diseases.

Sign in / Sign up

Export Citation Format

Share Document