scholarly journals The Step Further to Understand the Role of Cytosolic Phospholipase A2Alpha and Group X Secretory Phospholipase A2in Allergic Inflammation: Pilot Study

2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
Ewa Pniewska ◽  
Milena Sokolowska ◽  
Izabela Kupryś-Lipińska ◽  
Monika Przybek ◽  
Piotr Kuna ◽  
...  
Keyword(s):  
Protein Expression ◽  
Airway Inflammation ◽  
Bacterial Infections ◽  
A549 Cells ◽  
Allergic Inflammation ◽  
Cytosolic Phospholipase ◽  
Dust Mite ◽  
Der P1 ◽  
Immunoblotting Technique

Allergens, viral, and bacterial infections are responsible for asthma exacerbations that occur with progression of airway inflammation. cPLA2α and sPLA2X are responsible for delivery of arachidonic acid for production of eicosanoids—one of the key mediators of airway inflammation. However, cPLA2α and sPLA2X role in allergic inflammation has not been fully elucidated. The aim of this study was to analyze the influence of rDer p1 and rFel d1 and lipopolysaccharide (LPS) on cPLA2α expression and sPLA2X secretion in PBMC of asthmatics and in A549 cell line. PBMC isolated from 14 subjects, as well as A549 cells, were stimulated with rDer p1, rFel d1, and LPS. Immunoblotting technique was used to study the changes in cPLA2α protein expression and ELISA was used to analyze the release of sPLA2X. PBMC of asthmatics released more sPLA2X than those from healthy controls in the steady state. rDer p1 induced more sPLA2X secretion than cPLA2α protein expression. rFel d1 caused decrease in cPLA2α relative expression in PBMC of asthmatics and in A549 cells. Summarizing, Der p1 and Fel d1 involve phospholipase A2enzymes in their action. sPLA2X seems to be one of important PLA2isoform in allergic inflammation, especially caused by house dust mite allergens.

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 Tolerogenic Dendritic Cells Reduce Airway Inflammation in a Model of Dust Mite Triggered Allergic Inflammation

2018 ◽  
Vol 10 (4) ◽  
pp. 406 ◽  
Author(s):  
Luciana S. Aragão-França ◽  
Viviane C. J. Rocha ◽  
Andre Cronemberger-Andrade ◽  
F. H. B. Costa ◽  
José Fernandes Vasconcelos ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Airway Inflammation ◽  
Allergic Inflammation ◽  
Tolerogenic Dendritic Cells ◽  
Dust Mite

The Role of Chitin and TNF-Alpha in Airway Inflammation Induced By House Dust Mite in Murine Model

2014 ◽  
Vol 133 (2) ◽  
pp. AB400
Author(s):  
Sang Min Lee ◽  
Joon Pyo Choi ◽  
Young Min Kim ◽  
Seung Jin Choi ◽  
Hyun Taek Park ◽  
...  
Keyword(s):  
Airway Inflammation ◽  
House Dust ◽  
House Dust Mite ◽  
Murine Model ◽  
Tnf Alpha ◽  
Dust Mite

scholarly journals Enhanced Expression of IL-18 and IL-18BP in Plasma of Patients with Eczema: Altered Expression of IL-18BP and IL-18 Receptor on Mast Cells

2017 ◽  
Vol 2017 ◽  
pp. 1-12 ◽  
Author(s):  
Yalin Hu ◽  
Junling Wang ◽  
Huiyun Zhang ◽  
Hua Xie ◽  
Weiwei Song ◽  
...  
Keyword(s):  
Mast Cells ◽  
Fold Increase ◽  
Flow Cytometry Analysis ◽  
Altered Expression ◽  
House Dust Mite Allergen ◽  
Dust Mite ◽  
Enhanced Expression ◽  
Der P1 ◽  
Dust Mite Allergen

IL-18 has been found to be associated with eczema. However, little is known of the role of IL-18 binding protein (BP) and IL-18 receptor (R) in eczema. We therefore investigated the expression of IL-18, IL-18BP, and IL-18R on mast cells by using flow cytometry analysis and mouse eczema model. The results showed that plasma free IL-18 and free IL-18BP levels in eczema patients were higher than those in healthy controls. IL-18 provoked up to 3.1-fold increase in skin mast cells. IL-18 induced also an increase in IL-18BP+ mast cells, but a reduction of IL-18R+ mast cells in mouse eczema skin. It was found that house dust mite allergen Der p1 and egg allergen OVA induced upregulation of the expression of IL-18, IL-18BP, and IL-18R mRNAs in HMC-1 cells following 2 and 16 h incubation. In conclusion, correlation of IL-18 and IL-18BP in eczema plasma suggests an important balance between IL-18 and IL-18BP in eczema. The decrease in molar concentration ratio of plasma IL-18BP/IL-18 and allergen-induced upregulated expression of IL-18 and IL-18R in skin mast cells of the patients with eczema suggests that anti-IL-18 including IL-18BP therapy may be useful for the treatment of eczema.

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 Airway epithelial integrin β4 suppresses allergic inflammation by decreasing CCL17 production

2020 ◽  
Vol 134 (13) ◽  
pp. 1735-1749 ◽  
Author(s):  
Lin Yuan ◽  
Xun Zhang ◽  
Ming Yang ◽  
Xizi Du ◽  
Leyuan Wang ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Allergic Inflammation ◽  
Airway Epithelial Cells ◽  
Airway Epithelial ◽  
Th2 Response ◽  
Integrin Β4 ◽  
Dust Mite ◽  
Asthma Patients ◽  
Deficient Mice

Abstract Airway epithelial cells (AECs) play a key role in asthma susceptibility and severity. Integrin β4 (ITGB4) is a structural adhesion molecule that is down-regulated in the airway epithelium of asthma patients. Although a few studies hint toward the role of ITGB4 in asthmatic inflammation pathogenesis, their specific resultant effects remain unexplored. In the present study, we determined the role of ITGB4 of AECs in the regulation of Th2 response and identified the underpinning molecular mechanisms. We found that ITGB4 deficiency led to exaggerated lung inflammation and AHR with higher production of CCL17 in house dust mite (HDM)-treated mice. ITGB4 regulated CCL17 production in AECs through EGFR, ERK and NF-κB pathways. EFGR-antagonist treatment or the neutralization of CCL17 both inhibited exaggerated pathological marks in HDM-challenged ITGB4-deficient mice. Together, these results demonstrated the involvement of ITGB4 deficiency in the development of Th2 responses of allergic asthma by down-regulation of EGFR and CCL17 pathway in AECs.

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 Airway epithelial cell necroptosis contributes to asthma exacerbation in a mouse model of house dust mite-induced allergic inflammation

2021 ◽  
Author(s):  
Nikos Oikonomou ◽  
Martjin J. Schuijs ◽  
Antonis Chatzigiagkos ◽  
Ariadne Androulidaki ◽  
Vassilis Aidinis ◽  
...  
Keyword(s):  
Cell Death ◽  
Epithelial Cell ◽  
Mouse Model ◽  
House Dust ◽  
House Dust Mite ◽  
Airway Epithelial Cell ◽  
Allergic Inflammation ◽  
Airway Epithelial ◽  
Dust Mite

AbstractRegulation of epithelial cell death has emerged as a key mechanism controlling immune homeostasis in barrier surfaces. Necroptosis is a type of regulated necrotic cell death induced by receptor interacting protein kinase 3 (RIPK3) that has been shown to cause inflammatory pathologies in different tissues. The role of regulated cell death and particularly necroptosis in lung homeostasis and disease remains poorly understood. Here we show that mice with Airway Epithelial Cell (AEC)-specific deficiency of Fas-associated with death domain (FADD), an adapter essential for caspase-8 activation, developed exacerbated allergic airway inflammation in a mouse model of asthma induced by sensitization and challenge with house dust mite (HDM) extracts. Genetic inhibition of RIPK1 kinase activity by crossing to mice expressing kinase inactive RIPK1 as well as RIPK3 or MLKL deficiency prevented the development of exaggerated HDM-induced asthma pathology in FADDAEC-KO mice, suggesting that necroptosis of FADD-deficient AECs augmented the allergic immune response. These results reveal a role of AEC necroptosis in amplifying airway allergic inflammation and suggest that necroptosis could contribute to asthma exacerbations caused by respiratory virus infections inducing AEC death.

Role of house dust mite-derived extracellular vesicles in a murine model of airway inflammation

2018 ◽  
Vol 49 (2) ◽  
pp. 227-238 ◽  
Author(s):  
Jun-Pyo Choi ◽  
Seong Gyu Jeon ◽  
Yoon-Keun Kim ◽  
You Sook Cho
Keyword(s):  
Airway Inflammation ◽  
Extracellular Vesicles ◽  
House Dust ◽  
House Dust Mite ◽  
Murine Model ◽  
Dust Mite

scholarly journals Differential Regulation of Prostaglandin Production Mediated by Corticotropin-Releasing Hormone Receptor Type 1 and Type 2 in Cultured Human Placental Trophoblasts

Endocrinology ◽  
2008 ◽  
Vol 149 (6) ◽  
pp. 2866-2876 ◽  
Author(s):  
Lu Gao ◽  
Chunmei Lu ◽  
Chen Xu ◽  
Yi Tao ◽  
Binhai Cong ◽  
...  
Keyword(s):  
Protein Expression ◽  
Synthetic Enzymes ◽  
Cytosolic Phospholipase ◽  
Pge2 Release ◽  
Key Enzyme ◽  
Mrna And Protein Expression ◽  
Cox 2

Prostaglandin (PG) production by intrauterine tissues plays a key part in the control of pregnancy and parturition. The present study was to investigate the role of placenta-derived CRH and CRH-related peptides in the regulation of PG synthesis and metabolism. We found that placental trophoblasts expressed both CRH-R1 and CRH-R2. Treatment of cultured placental cells with either a CRH or urocortin I (UCNI) antibody resulted in a significant decrease in PGE2 release. Both CRH and UCNI antibodies significantly decreased mRNA and protein expression of synthetic enzymes cytosolic phospholipase A2 (cPLA2) and cyclooxygenase (COX)-2 and increased mRNA and protein expression of 15-hydroxyprostaglandin dehydrogenase (PGDH), the key enzyme of PG metabolism. CRH-R1/-R2 antagonist astressin and CRH-R1 antagonist antalarmin significantly inhibited PGE2 release, whereas CRH-R2 antagonist astressin-2b had no effect on PGE2 release. Administration of astressin decreased expression of cPLA2 but had no effect on COX-2 expression. Antalarmin reduced cPLA2 and COX-2 expression, whereas astressin-2b did not alter cPLA2 expression but increased COX-2 expression. PGDH expression was enhanced by these three antagonists. Cells treated with exogenous CRH and UCNI showed an increase in PGE2 release and expression of cPLA2 and COX-2 but a decrease in PGDH expression. UCNII and UCNIII had no effect on PGE2 release but decreased COX-2 and PGDH expression. Our results suggested CRH and CRH-related peptides act on CRH-R1 and CRH-R2 to exert different effects on PG biosynthetic enzymes cPLA2 and COX-2 and thereby modulate output of PGs from placenta, which would be important for controlling pregnancy and parturition.

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