Calcium ionophore-activated platelets induce eosinophil extracellular trap formation.

Background: Platelets play a modulatory role in inflammatory response by secreting a vast array of granules and disintegrating into membrane-bound microparticles upon activation. The interplay between eosinophils and platelets is postulated to be implicated in the pathology of allergic airway inflammation. In this study, we investigated whether activated platelets can induce eosinophil extracellular trap (EET) formation, a cellular process by which activated eosinophils release net-like DNA fibers.

Lysophosphatidylserine Induces MUC5AC Production via the Feedforward Regulation of the TACE-EGFR-ERK Pathway in Airway Epithelial Cells in a Receptor-Independent Manner.

Lysophosphatidylserine (LysoPS) is an amphipathic lysophospholipid that mediates a broad spectrum of inflammatory responses through a poorly characterized mechanism. Because LysoPS levels can rise in a variety of pathological conditions, we sought to investigate LysoPS's potential role in airway epithelial cells that actively participate in lung homeostasis. Here, we report a previously unappreciated function of LysoPS in production of a mucin component, MUC5AC, in the airway epithelial cells.

SERS biosensors for ultrasensitive detection of multiple biomarkers expressed in cancer cells.

The design and fabrication of multifunctional surface-enhanced Raman scattering (SERS) nanotags are key issues in their application to biological imaging of cells and tissues. In this study, highly sensitive, reproducible and long-term stable SERS nanotags were developed for the identification of localized distribution of multiple protein biomarkers expressed on breast cancer cells. To enhance the surface electromagnetic fields of Raman reporter molecules, Ag-encapsulated Au (Ag-Au) hollow nanospheres were synthesized.

Lysophosphatidylserine induces eosinophil extracellular trap formation and degranulation: Implications in severe asthma.

Background: Recent evidence demonstrates that activated eosinophils undergo a distinct form of lytic cell death, accompanied by formation of DNA-based eosinophil extracellular trap (EET) and degranulation, enhancing inflammatory immune responses in asthmatic airways. We previously showed that human blood eosinophils undergo degranulation in response to lysophosphatidylserine (LysoPS), an inflammatory lipid mediator, and strongly express P2Y10, a LysoPS receptor.

Methods: We evaluated EET, degranulation, and cell death of eosinophils in response to various concentrations of LysoPS.

Corrigendum: Eosinophil Activation by Toll-Like Receptor 4 Ligands Regulates Macrophage Polarization.

[This corrects the article DOI: 10.3389/fcell.2019.

Eosinophil Activation by Toll-Like Receptor 4 Ligands Regulates Macrophage Polarization.

Eosinophils are terminally differentiated granulocytes that have long been considered as destructive cells associated with Th2 type immune responses such as allergic inflammation and helminth infections. Recently, eosinophils have been actively studied as multifunctional leukocytes regulating an array of physiological responses through interaction with other immune cells. In this study, we examined the expression and function of Toll-like receptors (TLRs) in eosinophilic EoL-1 cells and demonstrated the expression of a number of immune mediators in activated EoL-1 cells and their interaction with the macrophage cell line THP-1 upon TLR4 ligand stimulation.

Inflammatory mediators ATP and S100A12 activate the NLRP3 inflammasome to induce MUC5AC production in airway epithelial cells.

Danger-associated molecular patterns (DAMPs) play a proinflammatory role in the pathogenesis of airway obstructive diseases such as severe asthma and chronic obstructive pulmonary disease. The NLRP3 inflammasome is a cytosolic multiprotein platform that activates the caspase-1 pathway in response to inflammatory stimuli such as DAMPs. ATP and S100 proteins are newly identified DAMPs that accumulate in inflamed airways.

Terminally Differentiating Eosinophils Express Neutrophil Primary Granule Proteins as well as Eosinophil-specific Granule Proteins in a Temporal Manner.

Neutrophils and eosinophils, 2 prominent granulocytes, are commonly derived from myelocytic progenitors through successive stages in the bone marrow. Our previous genome-wide transcriptomic data unexpectedly showed that genes encoding a multitude of neutrophil primary granule proteins (NPGPs) were markedly downregulated during the end period of eosinophilic terminal differentiation when cord blood (CB) cluster of differentiation (CD) 34 cells were induced to differentiate toward the eosinophil lineage during a 24-day culture period. Accordingly, this study aimed to examine whether NPGP genes were expressed on the way to eosinophil terminal differentiation stage and to compare their expression kinetics with that of genes encoding eosinophil-specific granule proteins (ESGPs).

GPNMB promotes proliferation of developing eosinophils.

Glycoprotein non-metastatic melanoma protein B (GPNMB) is a type I transmembrane protein that is expressed in a wide variety of cell types, including haematopoietic lineages. We previously demonstrated that GPNMB is one of the most highly expressed genes at an early and intermediate stage of eosinophil development. We herein examined GPNMB expression and its possible functional effect using cord blood (CB) CD34+ haematopoietic stem cells differentiating toward eosinophils during a 24-day culture period.

Aspirin induces IL-4 production: augmented IL-4 production in aspirin-exacerbated respiratory disease.

Aspirin hypersensitivity is a hallmark of aspirin-exacerbated respiratory disease (AERD), a clinical syndrome characterized by the severe inflammation of the respiratory tract after ingestion of cyclooxygenase-1 inhibitors. We investigated the capacity of aspirin to induce interleukin-4 (IL-4) production in inflammatory cells relevant to AERD pathogenesis and examined the associated biochemical and molecular pathways. We also compared IL-4 production in peripheral blood mononuclear cells (PBMCs) from patients with AERD vs aspirin-tolerant asthma (ATA) upon exposure to aspirin.

Roles of RUNX1 and PU.1 in CCR3 Transcription.

CCR3 is a chemokine receptor that mediates the accumulation of allergic inflammatory cells, including eosinophils and Th2 cells, at inflamed sites. The regulatory sequence of the CCR3 gene, contains two Runt-related transcription factor (RUNX) 1 sites and two PU.1 sites, in addition to a functional GATA site for transactivation of the CCR3 gene.

Olig2 is expressed late in human eosinophil development and controls Siglec-8 expression.

Oligodendrocyte transcription factor 2, a basic helix-loop-helix transcription factor that binds to E-box motifs, is known to have a key role in determining lineage specification of oligodendrocytes and motor neurons. In the present study, we report that oligodendrocyte transcription factor 2 is expressed in human eosinophils and involved in transcriptional activation of the gene encoding sialic acid binding immunoglobulin-like lectin 8 (Siglec-8), a late eosinophil-differentiation marker known to exert eosinophil apoptosis. When cord blood CD34 hematopoietic stem cells differentiated toward eosinophils during a 24-d culture period, oligodendrocyte transcription factor 2 protein was expressed in cord blood eosinophils on d 24, a time when cord blood eosinophils are considered fully differentiated, whereas it was not detectable on d 18 or at earlier time points.

Functional Characterization of Exonic Variants of the PPARGC1B Gene in Coregulation of Estrogen Receptor Alpha.

Peroxisome proliferator-activated receptor gamma coactivator 1 beta (PPARGC1B) is a coactivator of estrogen receptor (ER)α and ERβ. We previously demonstrated a significant association between a variant of exon 5 of the PPARGC1B gene (+102525 G>A, R265Q) and airway hyperreactivity (AHR). The aims of the study were to evaluate the genetic effects of variants of the PPARGC1B gene on the function of ERs.

Comparison of Proliferative Effect of Human Lactoferrin and Its Proteolytic Peptide on Normal and Transformed Epithelial Cells.

Human lactoferrin (hLF) is an iron-binding glycoprotein with a variety of functions. hLF undergoes proteolytic cleavage to smaller peptides in the stomach following ingestion. In the present study, we evaluated the effects of hLF and its proteolytic product, human lactoferrin peptide (hLFP), on the proliferation of two epithelial cells, HEK293 normal cells and KATO III gastric carcinoma cells, using an MTT assay and expression of proliferative nuclear cell antigen (PCNA), a notable proliferation marker.

Reduction of Nfia gene expression and subsequent target genes by binge alcohol in the fetal brain.

The objective of the present study was to investigate the changes in gene expression in the fetal brain (forebrain and hippocampus) caused by maternal binge alcohol consumption. Pregnant C57BL/6J mice were treated intragastrically with distilled phosphate-buffered saline (PBS) or ethanol (2.9 g/kg) from embryonic day (ED) 8-12.

Photo-crosslinkable hydrogel-based 3D microfluidic culture device.

We developed the photo-crosslinkable hydrogel-based 3D microfluidic device to culture neural stem cells (NSCs) and tumors. The photo-crosslinkable gelatin methacrylate (GelMA) polymer was used as a physical barrier in the microfluidic device and collagen type I gel was employed to culture NSCs in a 3D manner. We demonstrated that the pore size was inversely proportional to concentrations of GelMA hydrogels, showing the pore sizes of 5 and 25 w/v% GelMA hydrogels were 34 and 4 μm, respectively.

S100A8, S100A9 and S100A12 activate airway epithelial cells to produce MUC5AC via extracellular signal-regulated kinase and nuclear factor-κB pathways.

Airway mucus hyperproduction is a common feature of chronic airway diseases such as severe asthma, chronic obstructive pulmonary disease and cystic fibrosis, which are closely associated with neutrophilic airway inflammation. S100A8, S100A9 and S100A12 are highly abundant proteins released by neutrophils and have been identified as important biomarkers in many inflammatory diseases. Herein, we report a new role for S100A8, S100A9 and S100A12 for producing MUC5AC, a major mucin protein in the respiratory tract.

Use of surface-enhanced Raman scattering to quantify EGFR markers uninhibited by cetuximab antibodies.

Epidermal growth factor receptor (EGFR) has been recognized as an important prognostic marker expressed in cancer cells because its activation is associated with key features of cancer including tumor growth, survival, angiogenesis, and metastasis. Cetuximab is the first monoclonal antibody drug that targets EGFR overexpressed in cancer cells. It easily binds to EGFR, thereby down-regulating the receptor, blocking EGFR-mediated tyrosine kinase activity, and inhibiting cellular proliferation.

Elevation of S100 calcium binding protein A9 in sputum of neutrophilic inflammation in severe uncontrolled asthma.

Background: Neutrophilic airway inflammation is frequently observed in severe uncontrolled asthma (UA) and controlled asthma (CA). However, there is no sputum biomarker to differentiate the 2 conditions.

Objective: To identify biomarkers of severe uncontrolled asthma with neutrophilic airway inflammation.

Different GATA factors dictate CCR3 transcription in allergic inflammatory cells in a cell type-specific manner.

The chemokine receptor CCR3 is expressed in prominent allergic inflammatory cells, including eosinophils, mast cells, and Th2 cells. We previously identified a functional GATA element within exon 1 of the CCR3 gene that is responsible for GATA-1-mediated CCR3 transcription. Because allergic inflammatory cells exhibit distinct expression patterns of different GATA factors, we investigated whether different GATA factors dictate CCR3 transcription in a cell type-specific manner.

Epithelial-to-mesenchymal transition of human lung alveolar epithelial cells in a microfluidic gradient device.

Epithelial-to-mesenchymal transition (EMT), a process in which epithelial cells undergo phenotypic transitions to fibrotic cells, is induced by stimulants including transforming growth factor-beta1 (TGF-β1). In the present study, we developed a microfluidic gradient device to reproduce EMT in A549 human lung alveolar epithelial cells in response to TGF-β1 gradients. The device was directly mounted on the cells that had grown in cell culture plates and produced a stable concentration gradient of TGF-β1 with negligible shear stress, thereby providing a favorable environment for the anchorage-dependent cells.

Eosinophil development, regulation of eosinophil-specific genes, and role of eosinophils in the pathogenesis of asthma.

Eosinophils arise from hematopoietic CD34(+) stem cells in the bone marrow. They acquire IL-5Rα on their surface at a very early stage during eosinophilopoiesis, and differentiate under the strong influence of interleukin (IL)-5. They then exit to the bloodstream, and enter the lung upon exposure to airway inflammatory signals, including eotaxins.

Association analysis of formyl peptide receptor 2 (FPR2) polymorphisms and aspirin exacerbated respiratory diseases.

Aspirin-exacerbated respiratory diseases (AERD) are associated with the metabolism of arachidonic acid. FPR2 (formyl peptide receptor2) is a high-affinity ligand receptor for potent anti-inflammatory lipid metabolites: lipoxins. Thus, functional alterations of the FPR2 may contribute to AERD.

Association between WDR21A polymorphisms and airway responsiveness to inhaled corticosteroids in asthmatic patients.

Objective: Genetic polymorphism is partially responsible for the wide variation in the response of moderate-to-severe asthmatic patients to inhaled corticosteroids. The goal of the study was to examine polymorphisms in WDR21A, which encodes a putative glucocorticoid receptor (GR)-interacting protein, for their possible association with corticosteroid responsiveness.

Methods: The change in forced expiratory volume in 1 s [FEV(1) (ΔFEV(1))] induced by 4 weeks of inhaled treatment with fluticasone propionate (1000 µg daily) was measured in 230 asthmatic patients.

CpG methylation at GATA elements in the regulatory region of CCR3 positively correlates with CCR3 transcription.

DNA methylation may regulate gene expression by restricting the access of transcription factors. We have previously demonstrated that GATA-1 regulates the transcription of the CCR3 gene by dynamically interacting with both positively and negatively acting GATA elements of high affinity binding in the proximal promoter region including exon 1. Exon 1 has three CpG sites, two of which are positioned at the negatively acting GATA elements.