REV-ERBα agonist SR10067 attenuates Th2 cytokine-mediated barrier dysfunction in human bronchial epithelial cells.

Allergens and Th2 cytokines affect the homeostatic environment in the airways, leading to increased mucus production by goblet cells associated with altered adherens junctional complex (AJC) and tight junction (TJ) proteins responsible for maintaining epithelial barrier function. Circadian clock-dependent regulatory mechanisms such as inflammation and epithelial barrier function are gaining more attention due to their therapeutic potential against allergic inflammatory lung diseases. Currently, there are no studies to support whether REV-ERBα activation can attenuate Th2 cytokine-induced epithelial barrier dysfunction in human bronchial epithelial cells.

Environmental tobacco smoke exposure exaggerates bleomycin-induced collagen overexpression during pulmonary fibrogenesis.

Environmental tobacco smoke (ETS) is known to cause lung inflammatory and injurious responses. Smoke exposure is associated with the pathobiology related to lung fibrosis, whereas the mechanism that ETS exposure augments pulmonary fibrogenesis is unclear. We hypothesized that ETS exposure could exacerbate fibrotic responses via collagen dynamic dysregulation and complement activation.

Environmental tobacco smoke exposure exaggerates bleomycin- induced collagen overexpression during pulmonary fibrogenesis.

Environmental tobacco smoke (ETS) is known to cause lung inflammatory and injurious responses. Smoke exposure is associated with the pathobiology related to lung fibrosis, whereas the mechanism by which ETS exposure augments lung fibrogenesis is unclear. We hypothesized that ETS exposure could exacerbate fibrotic responses via collagen dynamic dysregulation and complement activation.

Lung mechanics showing sex-based differences and circadian time-of-day response to bleomycin-induced lung injury in mice.

Idiopathic pulmonary fibrosis (IPF) is a progressive disease that impairs lung mechanical properties due to dysregulated extracellular matrix remodeling. Lung function assessment is an important physiological endpoint in the mouse model of pulmonary fibrosis (PF) that has gained a broader scientific acceptance in the field. IPF pathophysiology shows sex-based differences, disproportionately affecting more men compared to women.

Acute HDM exposure shows time-of-day and sex-based differences in the severity of lung inflammation and circadian clock disruption.

Background: Asthma is a chronic inflammatory disease that shows a time-of-day response to variations in symptoms/severity. However, how the lung circadian clock influences time-of-day response and sex-based differences in house dust mite (HDM)-induced airway inflammation and remodeling has not been thoroughly investigated.

Objective: We sought to determine whether acute HDM exposure in wild-type mice shows time-of-day response and sex-based differences in allergic airway inflammation and circadian clock disruption in the lungs.

Chronic HDM exposure shows time-of-day and sex-based differences in inflammatory response associated with lung circadian clock disruption.

Circadian rhythms and sex differences are involved in the pathophysiology of asthma. Yet, there are no reports that simultaneously address the role of the circadian clock and sex-based differences in chronic house dust mite (HDM)-induced asthma. Here, we sought to determine if chronic HDM exposure during the resting phase (zeitgeber time: ZT0/6:00 a.

Rev-erbα agonists suppresses TGFβ1-induced fibroblast-to-myofibroblast transition and pro-fibrotic phenotype in human lung fibroblasts.

Idiopathic pulmonary fibrosis (IPF) is an interstitial lung disease characterized by excessive scarring of the lungs that can lead to respiratory failure and death. Lungs of patients with IPF demonstrate excessive deposition of extracellular matrix (ECM) and an increased presence of pro-fibrotic mediators such as transforming growth factor-beta 1 (TGFβ1), which is a major driver of fibroblast-to-myofibroblast transition (FMT). Current literature supports that circadian clock dysfunction plays an essential role in the pathophysiology of various chronic inflammatory lung diseases such as asthma, chronic obstructive pulmonary disease, and IPF.

Acute and Repeated Ozone Exposures Differentially Affect Circadian Clock Gene Expression in Mice.

Circadian rhythms have an established role in regulating physiological processes, such as inflammation, immunity, and metabolism. Ozone, a common environmental pollutant with strong oxidative potential, is implicated in lung inflammation/injury in asthmatics. However, whether O exposure affects the expression of circadian clock genes in the lungs is not known.

House dust mite and Th2 cytokine-mediated epithelial barrier dysfunction attenuation by KL001 in 16-HBE cells.

House dust mite (HDM) is a common aeroallergen that can disrupt the airway epithelial barrier leading to dysregulated immune response, resulting in allergic lung diseases such as asthma. Cryptochrome (CRY), a circadian clock gene, plays an important role in the regulation of metabolism, and immune response. It remains unclear whether stabilizing CRY using KL001 can attenuate HDM/Th2 cytokine-induced epithelial barrier dysfunction in 16-HBE cells.

Circadian clock molecule REV-ERBα regulates lung fibrotic progression through collagen stabilization.

Molecular clock REV-ERBα is central to regulating lung injuries, and decreased REV-ERBα abundance mediates sensitivity to pro-fibrotic insults and exacerbates fibrotic progression. In this study, we determine the role of REV-ERBα in fibrogenesis induced by bleomycin and Influenza A virus (IAV). Bleomycin exposure decreases the abundance of REV-ERBα, and mice dosed with bleomycin at night display exacerbated lung fibrogenesis.

Circadian Disruption in Night Shift Work and Its Association with Chronic Pulmonary Diseases.

Globalization and the expansion of essential services over continuous 24 h cycles have necessitated the adaptation of the human workforce to shift-based schedules. Night shift work (NSW) causes a state of desynchrony between the internal circadian machinery and external environmental cues, which can impact inflammatory and metabolic pathways. The discovery of clock genes in the lung has shed light on potential mechanisms of circadian misalignment in chronic pulmonary disease.

Current Perspective on the Role of the Circadian Clock and Extracellular Matrix in Chronic Lung Diseases.

The circadian clock is a biochemical oscillator that rhythmically regulates physiological and behavioral processes such as inflammation, immunity, and metabolism in mammals. Circadian clock disruption is a key driver for chronic inflammatory as well as fibrotic lung diseases. While the mechanism of circadian clock regulation in the lung has been minimally explored, some evidence suggests that the transforming growth factor β (TGFβ) signaling pathway and subsequent extracellular matrix (ECM) accumulation in the lung may be controlled via a clock-dependent mechanism.

Circadian clock-based therapeutics in chronic pulmonary diseases.

The circadian clock is the biochemical oscillator that orchestrates the observable circadian rhythms in physiology and behavior. Disruption of the circadian clock in the lungs during chronic pulmonary diseases is considered one of the key etiological risk factors that drive pathobiology. Preclinical studies support that pharmacological manipulation of the circadian clock is a conceivable approach for the development of novel clock-based therapeutics.

Circadian molecular clock disruption in chronic pulmonary diseases.

The circadian clock is the biochemical oscillator with a near 24-h period that is responsible for generating the circadian rhythms in peripheral organs including the lung. Mounting evidence suggests that circadian clock disruption during chronic lung diseases plays an essential role in augmented oxidative stress, inflammatory response, metabolic imbalances, hypoxia/hyperoxia, mucus secretion, dysregulated autophagy, and alters pulmonary function. Here, we review circadian clock disruption and discuss candidate clock genes that are altered at the transcriptional or translational level in chronic pulmonary diseases.

Evaluation of stable reference genes for qPCR normalization in circadian studies related to lung inflammation and injury in mouse model.

Circadian rhythms have a profound effect on lung function and immune-inflammatory response in chronic airway diseases. Thus, understanding the molecular mechanisms of circadian gene expression of core clock-controlled genes (CCGs) may help better understand how it contributes to the physiology and pathology of lung diseases. Ongoing studies have been analyzing gene expression levels of CCGs in mouse lungs using quantitative real-time PCR (qRT-PCR).

Recent updates on the role of extracellular vesicles in the pathogenesis of allergic asthma.

Asthma is a chronic inflammatory disease of the airway diagnosed with different endotypes and phenotypes, characterized by airway obstruction in response to allergens, bacterial/viral infections, or pollutants. Several cell types such as the airway epithelial cells, mesenchymal stem cells and different immune cells including dendritic cells (DCs), T and B cells and mast cells play an essential role during the pathobiology of asthma. Extracellular vesicles (EVs) are membranous nanovesicles produced by every cell type that facilitates intercellular communications.