Nrf2 Deficiency Accelerates IL-17-Dependent Neutrophilic Airway Inflammation in Asthmatic Mice.

Asthma is a heterogeneous disease that can be broadly classified into type 2, which is primarily steroid-sensitive and eosinophilic, and non-type 2, which is primarily steroid-resistant and neutrophilic. While the mechanisms leading to the development of molecular-targeted therapies for type 2 asthma are being elucidated, much remains to be learned about non-type 2 asthma. To investigate the role of oxidative stress in refractory allergic airway inflammation, we compared asthma models generated by immunizing wild-type and nuclear factor erythroid-2-related factor 2 (Nrf2)-deficient mice with the house dust mite antigen.

ELOVL6 deficiency aggravates allergic airway inflammation through the ceramide-S1P pathway in mice.

Background: Elongation of very-long-chain fatty acids protein 6 (ELOVL6), an enzyme regulating elongation of saturated and monounsaturated fatty acids with C12 to C16 to those with C18, has been recently indicated to affect various immune and inflammatory responses; however, the precise process by which ELOVL6-related lipid dysregulation affects allergic airway inflammation is unclear.

Objectives: This study sought to evaluate the biological roles of ELOVL6 in allergic airway responses and investigate whether regulating lipid composition in the airways could be an alternative treatment for asthma.

Methods: Expressions of ELOVL6 and other isoforms were examined in the airways of patients who are severely asthmatic and in mouse models of asthma.

Regulates the Development of Ovalbumin-Induced Airway Remodeling and Steroid Insensitivity in Mice.

is a member of the gene family encoding the hyaluronan synthase 2, which can generate high-molecular-weight hyaluronan (HMW-HA). Our previous study identified as a candidate gene for increased susceptibility to adult asthma. However, whether dysfunction affects airway remodeling and steroid insensitivity is still limited.

ROS-Nrf2 pathway mediates the development of TGF-β1-induced epithelial-mesenchymal transition through the activation of Notch signaling.

Epithelial-mesenchymal transition (EMT) is a cellular process by which epithelial cells transform to acquire mesenchymal phenotypes. Accumulating evidence indicate the involvement of EMT in the progression of malignant diseases. Notch signaling mediates TGF-β1-induced EMT through direct transcriptional activation of Snai1.

Depletion of PD-1 or PD-L1 did not affect the mortality of mice infected with Mycobacterium avium.

The programmed cell death-1 (PD-1) and programmed cell death-ligand 1 (PD-L1) pathway could affect antimicrobial immune responses by suppressing T cell activity. Several recent studies demonstrated that blocking of the PD-1/PD-L1 pathway exacerbated Mycobacterium tuberculosis infection. However, the effect of blocking this pathway in pulmonary Mycobacterium avium-intracellulare complex (MAC) infection is not fully understood.

Negative-pressure pulmonary Hemorrhaging Due to Severe Obstructive Sleep Apnea.

A 24-year-old man with a history of bloody sputum for 6 months was referred to our hospital with suspected alveolar hemorrhaging due to vasculitis. Chest computed tomography showed ground-glass opacities in both lungs, and an examination of his bronchoalveolar lavage fluid showed alveolar hemorrhaging. However, no evidence of vasculitis was found, and subsequent polysomnographic testing confirmed that he had severe obstructive sleep apnea (OSA).

Nrf2 Regulates Granuloma Formation and Macrophage Activation during Mycobacterium avium Infection via Mediating Nramp1 and HO-1 Expressions.

Nrf2 is a redox-sensitive transcription factor that is thought to be important in protection against intracellular pathogens. To determine the protective role of Nrf2 in the host defense against complex (MAC), both wild-type and -deficient mice were intranasally infected with MAC bacteria. -deficient mice were highly susceptible to MAC bacteria compared with wild-type mice.

Small-Cell Lung Cancer Treatment of Newly Diagnosed Patients with Poor Performance Status.

Small-cell lung cancer (SCLC) is highly sensitive to platinum-based chemotherapy. However, its indication in patients with a poor performance status (PS) at initial diagnosis is controversial. We retrospectively reviewed all clinical courses of pathologically diagnosed SCLC patients with poor PS, Eastern Cooperative Oncology Group PS 3 and 4.

Transcription Factor T-bet Attenuates the Development of Elastase-induced Emphysema in Mice.

Chronic obstructive pulmonary disease (COPD) is a progressive lung disease characterized by peripheral airways inflammation and emphysema. Emerging evidence indicates a contribution of both innate and adaptive immune cells to the development of COPD. Transcription factor T-bet modulates the function of immune cells and therefore might be involved in the pathogenesis of COPD.

pneumonia with hemoptysis: A case report.

, which colonizes upper respiratory and digestive tracts, is a leading cause of respiratory diseases in many host species. Here, we describe a case of pneumonia with hemoptysis. A 72-year-old female diagnosed with bronchiectasis with a 36-year history presented with a worsened infiltrative and granular shadow in the lower right lobe and lingular segment.

Sulforaphane ameliorates steroid insensitivity through an Nrf2-dependent pathway in cigarette smoke-exposed asthmatic mice.

Oxidative stress induced by cigarette smoke and other environmental pollutants contributes to refractory asthma. To better understand the role of smoking in asthma, we investigated the effects of cigarette smoke on allergic airway responses in mice and examined expression of nuclear factor-E2-related factor-2 (Nrf2) and its downstream factors, because Nrf2 is known to play a pivotal role in antioxidant responses. OVA-sensitized and challenged BALB/c mice were exposed to cigarette smoke and then treated with dexamethasone, sulforaphane (an activator of Nrf2), or their combination.

Notch signaling regulates cell density-dependent apoptosis of NIH 3T3 through an IL-6/STAT3 dependent mechanism.

Apoptosis is a physiological process that plays a critical maintenance role in cellular homeostasis. Previous reports have demonstrated that cells undergo apoptosis in a cell density-dependent manner, which is regulated, in part, by signal transducers and activators of transcription (STAT) 3. The molecular mechanisms regulating cell density-dependent apoptosis, however, has not been thoroughly investigated to date.

Airway glycomic and allergic inflammatory consequences resulting from keratan sulfate galactose 6-O-sulfotransferase (CHST1) deficiency.

Siglec-F is a pro-apoptotic receptor on mouse eosinophils that recognizes 6'-sulfated sialyl Lewis X and 6'-sulfated sialyl N-acetyl-lactosamine as well as multivalent sialyl N-acetyl-lactosamine structures on glycan arrays. We hypothesized that attenuation of the carbohydrate sulfotransferase 1 (CHST1) gene encoding keratan sulfate galactose 6-O-sulfotransferase, an enzyme likely required for 6'-sulfation of some of these putative Siglec-F glycan ligands, would result in decreased Siglec-F lung ligand levels and enhanced allergic eosinophilic airway inflammation. Tissue analysis detected CHST1 expression predominantly not only in parenchymal cells but not in airway epithelium, the latter being a location where Siglec-F ligands are located.

Paraneoplastic limbic encephalitis with late-onset magnetic resonance imaging findings: A case report.

Paraneoplastic limbic encephalitis (PLE), a paraneoplastic neurological syndrome (PNS), is a rare nervous system disorder that results from the indirect effects of tumors and is commonly associated with small-cell lung cancer (SCLC). Previous studies have reported that magnetic resonance imaging (MRI) may be useful for diagnosing LE. Temporal lobe abnormalities are observed using T2-weighted and fluid-attenuated inversion recovery sequences; however, such abnormalities are detected in only 60% of patients with PLE.

Landiolol hydrochloride ameliorates acute lung injury in a rat model of early sepsis through the suppression of elevated levels of pulmonary endothelin-1.

Among the dysfunctions and pathologies associated with sepsis, the underlying molecular mechanisms of sepsis-induced acute lung injury (ALI) are poorly understood. Endothelin (ET)-1, a potent vasoconstrictor and pro-inflammatory peptide, is known to be involved in the pathogenesis of ALI in a rat model of sepsis. Here, we investigated whether landiolol hydrochloride, an ultra-short-acting β-blocker, plays a crucial role in ameliorating and attenuating LPS-induced ALI through modulation of the ET-1 system.

Endogenous airway mucins carry glycans that bind Siglec-F and induce eosinophil apoptosis.

Background: Sialic acid-binding, immunoglobulin-like lectin (Siglec) F is a glycan-binding protein selectively expressed on mouse eosinophils. Its engagement induces apoptosis, suggesting a pathway for ameliorating eosinophilia in the setting of asthma and other eosinophil-associated diseases. Siglec-F recognizes sialylated sulfated glycans in glycan-binding assays, but the identities of endogenous sialoside ligands and their glycoprotein carriers in vivo are unknown.

Mice deficient in the St3gal3 gene product α2,3 sialyltransferase (ST3Gal-III) exhibit enhanced allergic eosinophilic airway inflammation.

Background: Sialic acid-binding immunoglobulin-like lectin (Siglec)-F is a proapoptotic receptor on mouse eosinophils, but little is known about its natural tissue ligand.

Objective: We previously reported that the St3gal3 gene product α2,3 sialyltransferase (ST3Gal-III) is required for constitutive Siglec-F lung ligand synthesis. We therefore hypothesized that attenuation of ST3Gal-III will decrease Siglec-F ligand levels and enhance allergic eosinophilic airway inflammation.

The role of lung epithelial ligands for Siglec-8 and Siglec-F in eosinophilic inflammation.

Purpose Of Review: Siglec-8 and Siglec-F are single pass transmembrane inhibitory receptors found on the surface of human and mouse eosinophils, respectively, but very little is known about their physiologic glycan ligands. This article reviews the latest knowledge on this topic and outlines the strategies being used to further define the production and glycobiochemical nature of these molecules in the lung.

Recent Findings: Both Siglec-8 and Siglec-F recognize the same glycan structure, namely 6'-sulfated sialyl Lewis X, as determined using glycan array technologies.