Involvement of the Constitutive Photomorphogenesis 9 Signalosome Subunit 5 With Programmed Cell Death Protein 1 Ligand in Asthma.

PURPOSE: The constitutive photomorphogenesis 9 signalosome (CSN) is a highly conserved protein complex comprised of eight subunits, each of which play crucial roles in diverse cellular processes, such as signal transduction, gene transcription, angiogenesis, and cell proliferation. In the context of asthma, a potential emerging target is the programmed death-ligand 1 (PD-L1)-mediated pathway, which serves as a significant immune checkpoint inhibitor in this condition. However, the precise involvement of CSN subunit 5 (CSN5) in bronchial asthma and the interplay between CSN5 and PD-L1 in asthma remain poorly understood. METHODS: The potential association between CSN5 and bronchial asthma was explored in a mouse model of ovalbumin (OVA)-induced asthma. Samples were obtained from human lung microvascular endothelial cell (HMVEC-L) treated with Dermatophagoides pteronyssinus (Der p 1) and CSN5 small interfering RNA. The expression of nuclear factor (NF)-κB, IκBα, inhibitor of κB kinase ß (IKKß), PD-L1, and CSN5 was assessed. Additionally, plasma CSN5 levels in asthma patients, both in stable and exacerbated states, were examined. RESULTS: Plasma levels of CSN5 were elevated in patients with exacerbated asthma (n = 19) compared to both healthy controls (n = 10) and patients with stable asthma (n = 19). The CSN5 level demonstrated a correlation with lung function in individuals with asthma. Silencing CSN5 in HMVEC-L led to a reduction in NF-κB protein levels at 4 hours and PD-L1 levels at 4, 8, and 24 hours after Der p 1 treatment. In OVA-sensitized/challenged mice, goblet cell hyperplasia, lung fibrosis, and the levels of CSN5, PD-L1, interleukin-13, interferon-γ, phospho (p)-NF-κB, p-IκBα, and p-IKKß proteins increased at 33 and 80 days compared to control mice. However, these changes were mitigated by treatment with a PD-L1 inhibitor. CONCLUSIONS: These findings suggest that CSN5, along with PD-L1, could serve as a promising target for the treatment of asthma.

The Effect of Green Tea Extract on Pulmonary Inflammation in Nanoparticles-Exposed Mice.

SCOPE: Titanium dioxide nanoparticles (TiO2 NPs) are air pollutants that exacerbate chronic respiratory diseases such as asthma and Chronic Obstructive Pulmonary Disease (COPD) However, little is known about the mechanism underlying the antipollutant effects of green tea extract (GTE). This study evaluates the efficacy and mechanism of GTE on lung inflammation and fibrosis in mice exposed to TiO2 NPs. METHODS AND RESULTS: The TiO2 NPs model is induced by having mice inhale TiO2 NPs, while controls receive an equivalent volume of saline. Treatment with oral GTE is initiated after TiO2 NPs inhalation and is given once daily for 4 weeks. Airway resistance and pulmonary inflammation are increased in mice exposed to TiO2 NPs. GTE treatment reduces the airway inflammation and airway resistance, and attenuates the pathological changes including lung fibrosis compared to the mice exposed to TiO2 NPs. With GTE, there are no significant increases in cytokines and immunoglobulin E (IgE) in mice exposed to TiO2 NPs. GTE inhibits matrix metalloproteinases (MMPs) and apoptotic factors induced by TiO2 NPs exposure, and these protective effects of GTE are closely related to the mitogen-activated protein kinase (MAPK) signaling pathway. CONCLUSION: GTE modulates pulmonary inflammation in mice exposed to air pollutants, suggesting that GTE may be beneficial in respiratory diseases exacerbated by such pollutants.

Impact of the Junction Adhesion Molecule-A on Asthma.

PURPOSE: Junctional adhesion molecule (JAM)-A is an immunoglobulin-like molecule that colocalizes with tight junctions (TJs) in the endothelium and epithelium. It is also found in blood leukocytes and platelets. The biological significance of JAM-A in asthma, as well as its clinical potential as a therapeutic target, are not well understood. The aim of this study was to elucidate the role of JAM-A in a mouse model of asthma, and to determine blood levels of JAM-A in asthmatic patients. MATERIALS AND METHODS: Mice sensitized and challenged with ovalbumin (OVA) or saline were used to investigate the role of JAM-A in the pathogenesis of bronchial asthma. In addition, JAM-A levels were measured in the plasma of asthmatic patients and healthy controls. The relationships between JAM-A and clinical variables in patients with asthma were also examined. RESULTS: Plasma JAM-A levels were higher in asthma patients (n=19) than in healthy controls (n=12). In asthma patients, the JAM-A levels correlated with forced expiratory volume in 1 second (FEV1%), FEV1/forced vital capacity (FVC), and the blood lymphocyte proportion. JAM-A, phospho-JNK, and phospho-ERK protein expressions in lung tissue were significantly higher in OVA/OVA mice than in control mice. In human bronchial epithelial cells treated with house dust mite extracts for 4 h, 8 h, and 24 h, the JAM-A, phospho-JNK, and phospho-ERK expressions were increased, as shown by Western blotting, while the transepithelial electrical resistance was reduced. CONCLUSION: These results suggest that JAM-A is involved in the pathogenesis of asthma, and may be a marker for asthma.

Risk assessment of polycyclic aromatic hydrocarbons in meat and edible oils: results of a total diet study in South Korea.

Polycyclic aromatic hydrocarbons (PAHs) constitute carcinogens. In this study, the risk of PAHs being consumed through meat and edible oils was assessed using a total diet study. Results were monitored by applying the toxic equivalency factor of benzo[a]pyrene; among each category, this factor was highest in grilled beef chitterlings (1.35 µg/kg), grilled Wiener sausages (1.20 µg/kg), fried chicken wings (0.70 µg/kg), and stir-fried perilla oil (1.29 µg/kg). The chronic daily intake was calculated, and risk characterization was estimated by applying the margin of exposure using the benchmark dose approach. Most samples analyzed in our study were denoted as having no concern; however, the intake group of stir-fried beef chitterlings, pan-fried pink sausage, deep-fried pork loin, and grilled duck was regarded as possible concern, and grilled chicken was assessed as having low concern. PAH changes must be monitored on a regular basis. Supplementary Information: The online version contains supplementary material available at 10.1007/s10068-022-01137-5.