scholarly journals Protective Features of Autophagy in Pulmonary Infection and Inflammatory Diseases

Cells ◽  
2019 ◽  
Vol 8 (2) ◽  
pp. 123 ◽  
Author(s):  
Kui Wang ◽  
Yi Chen ◽  
Pengju Zhang ◽  
Ping Lin ◽  
Na Xie ◽  
...  
Keyword(s):  
Pulmonary Infection ◽  
Inflammatory Responses ◽  
Inflammatory Diseases ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Autophagy Pathway ◽  
Pulmonary Arterial ◽  
Cellular Components ◽  
Cellular Stressors

Autophagy is a highly conserved catabolic process involving autolysosomal degradation of cellular components, including protein aggregates, damaged organelles (such as mitochondria, endoplasmic reticulum, and others), as well as various pathogens. Thus, the autophagy pathway represents a major adaptive response for the maintenance of cellular and tissue homeostasis in response to numerous cellular stressors. A growing body of evidence suggests that autophagy is closely associated with diverse human diseases. Specifically, acute lung injury (ALI) and inflammatory responses caused by bacterial infection or xenobiotic inhalation (e.g., chlorine and cigarette smoke) have been reported to involve a spectrum of alterations in autophagy phenotypes. The role of autophagy in pulmonary infection and inflammatory diseases could be protective or harmful dependent on the conditions. In this review, we describe recent advances regarding the protective features of autophagy in pulmonary diseases, with a focus on ALI, idiopathic pulmonary fibrosis (IPF), chronic obstructive pulmonary disease (COPD), tuberculosis, pulmonary arterial hypertension (PAH) and cystic fibrosis.

scholarly journals The emerging role of C/EBPs in glucocorticoid signaling: lessons from the lung

2011 ◽  
Vol 212 (3) ◽  
pp. 291-305 ◽  
Author(s):  
Abraham B Roos ◽  
Magnus Nord
Keyword(s):  
Transcription Factors ◽  
Potential Role ◽  
Current Knowledge ◽  
Inflammatory Diseases ◽  
Steroid Resistance ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Glucocorticoid Signaling ◽  
Enhancer Binding Protein

Glucocorticoids (GCs) have been successfully used in the treatment of inflammatory diseases for decades. However, there is a relative GC resistance in several inflammatory lung disorders, such as chronic obstructive pulmonary disease (COPD), but still the mechanism(s) behind this unresponsiveness remains unknown. Interaction between transcription factors and the GC receptor contribute to GC effects but may also provide mechanisms explaining steroid resistance. CCAAT/enhancer-binding protein (C/EBP) transcription factors are important regulators of pulmonary gene expression and have been implicated in inflammatory lung diseases such as asthma, pulmonary fibrosis, cystic fibrosis, sarcoidosis, and COPD. In addition, several studies have indicated a role for C/EBPs in mediating GC effects. In this review, we discuss the different mechanisms of GC action as well as the function of the lung-enriched members of the C/EBP transcription factor family. We also summarize the current knowledge of the role of C/EBP transcription factors in mediating the effects of GCs, with emphasis on pulmonary effects, and their potential role in mediating GC resistance.

scholarly journals Interleukin-36 Cytokines in Infectious and Non-Infectious Lung Diseases

2021 ◽  
Vol 12 ◽  
Author(s):  
Hernán F. Peñaloza ◽  
Rick van der Geest ◽  
Joel A. Ybe ◽  
Theodore J. Standiford ◽  
Janet S. Lee
Keyword(s):  
Infectious Diseases ◽  
Lung Diseases ◽  
Skin Diseases ◽  
Inflammatory Diseases ◽  
Lymphoid Cells ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Inflammatory Conditions ◽  
Inflammatory Processes

The IL-36 family of cytokines were identified in the early 2000’s as a new subfamily of the IL-1 cytokine family, and since then, the role of IL-36 cytokines during various inflammatory processes has been characterized. While most of the research has focused on the role of these cytokines in autoimmune skin diseases such as psoriasis and dermatitis, recent studies have also shown the importance of IL-36 cytokines in the lung inflammatory response during infectious and non-infectious diseases. In this review, we discuss the biology of IL-36 cytokines in terms of how they are produced and activated, as well as their effects on myeloid and lymphoid cells during inflammation. We also discuss the role of these cytokines during lung infectious diseases caused by bacteria and influenza virus, as well as other inflammatory conditions in the lungs such as allergic asthma, lung fibrosis, chronic obstructive pulmonary disease, cystic fibrosis and cancer. Finally, we discuss the current therapeutic advances that target the IL-36 pathway and the possibility to extend these tools to treat lung inflammatory diseases.

scholarly journals The Role of Macrophages in the Development of Acute and Chronic Inflammatory Lung Diseases

Cells ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 897
Author(s):  
Jae-Won Lee ◽  
Wanjoo Chun ◽  
Hee Jae Lee ◽  
Jae-Hong Min ◽  
Seong-Man Kim ◽  
...  
Keyword(s):  
Allergic Asthma ◽  
Lung Diseases ◽  
Inflammatory Responses ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Adaptive Immune ◽  
Activation Of Transcription ◽  
Organ Systems ◽  
Underlying Mechanisms

Macrophages play an important role in the innate and adaptive immune responses of organ systems, including the lungs, to particles and pathogens. Cumulative results show that macrophages contribute to the development and progression of acute or chronic inflammatory responses through the secretion of inflammatory cytokines/chemokines and the activation of transcription factors in the pathogenesis of inflammatory lung diseases, such as acute lung injury (ALI), acute respiratory distress syndrome (ARDS), ARDS related to COVID-19 (coronavirus disease 2019, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)), allergic asthma, chronic obstructive pulmonary disease (COPD), and idiopathic pulmonary fibrosis (IPF). This review summarizes the functions of macrophages and their associated underlying mechanisms in the development of ALI, ARDS, COVID-19-related ARDS, allergic asthma, COPD, and IPF and briefly introduces the acute and chronic experimental animal models. Thus, this review suggests an effective therapeutic approach that focuses on the regulation of macrophage function in the context of inflammatory lung diseases.

scholarly journals IL-17 Aggravates Pseudomonas aeruginosa Airway Infection in Acute Exacerbations of Chronic Obstructive Pulmonary Disease

2022 ◽  
Vol 12 ◽  
Author(s):  
Fengming Ding ◽  
Lei Han ◽  
Qiang Fu ◽  
Xinxin Fan ◽  
Rong Tang ◽  
...  
Keyword(s):  
Mouse Models ◽  
Inflammatory Cytokine ◽  
Inflammatory Responses ◽  
Neutralizing Antibody ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Airway Infection ◽  
Copd Patients ◽  
Acute Exacerbations

Pseudomonas aeruginosa airway infection increases risks of exacerbations and mortality in chronic obstructive pulmonary disease (COPD). We aimed to elucidate the role of IL-17 in the pathogenesis. We examined the expression and influences of IL-23/IL-17A in patients with stable COPD (n = 33) or acute COPD exacerbations with P. aeruginosa infection (n = 34). A mouse model of COPD (C57BL/6) was used to investigate the role of IL-17A in host inflammatory responses against P. aeruginosa infection through the application of IL-17A–neutralizing antibody or recombinant IL-17A. We found that P. aeruginosa infection increased IL-23/17A signaling in lungs of both COPD patients and COPD mouse models. When COPD mouse models were treated with neutralizing antibody targeting IL-17A, P. aeruginosa induced a significantly less polymorphonuclear leukocyte infiltration and less bacterial burden in their lungs compared to those of untreated counterparts. The lung function was also improved by neutralizing antibody. Furthermore, IL-17A-signaling blockade significantly reduced the expression of pro-inflammatory cytokine IL-1β, IL-18, TNF-α, CXCL1, CXCL15 and MMP-9, and increased the expression of anti-inflammatory cytokine IL-10 and IL-1Ra. The application of mouse recombinant IL-17A exacerbated P. aeruginosa-mediated inflammatory responses and pulmonary dysfunction in COPD mouse models. A cytokine protein array revealed that the expression of retinol binding protein 4 (RBP4) was down-regulated by IL-17A, and exogenous RBP4-recombinant protein resulted in a decrease in the severity of P. aeruginosa-induced airway dysfunction. Concurrent application of IL-17A-neutralizing antibody and ciprofloxacin attenuated airway inflammation and ventilation after inoculation of P. aeruginosa in COPD mouse models. Our results revealed that IL-17 plays a detrimental role in the pathogenesis of P. aeruginosa airway infection during acute exacerbations of COPD. Targeting IL-17A is a potential therapeutic strategy in controlling the outcomes of P. aeruginosa infection in COPD patients.

scholarly journals Microbiota: A Missing Link in The Pathogenesis of Chronic Lung Inflammatory Diseases

2021 ◽  
Vol 70 (1) ◽  
pp. 25-32
Author(s):  
AGNIESZKA MAGRYŚ
Keyword(s):  
Respiratory Diseases ◽  
Inflammatory Diseases ◽  
Chronic Obstructive ◽  
High Morbidity ◽  
Obstructive Pulmonary Disease ◽  
Chronic Respiratory Diseases ◽  
Chronic Pulmonary Diseases ◽  
Underlying Mechanisms

Chronic respiratory diseases account for high morbidity and mortality, with asthma, chronic obstructive pulmonary disease (COPD), and cystic fibrosis (CF) being the most prevalent globally. Even though the diseases increase in prevalence, the exact underlying mechanisms have still not been fully understood. Despite their differences in nature, pathophysiologies, and clinical phenotypes, a growing body of evidence indicates that the presence of lung microbiota can shape the pathogenic processes underlying chronic inflammation, typically observed in the course of the diseases. Therefore, the characterization of the lung microbiota may shed new light on the pathogenesis of these diseases. Specifically, in chronic respiratory tract diseases, the human microbiota may contribute to the disease’s development and severity. The present review explores the role of the microbiota in the area of chronic pulmonary diseases, especially COPD, asthma, and CF.

scholarly journals Role of the Arylhydrocarbon Receptor (AhR) in the Pathology of Asthma and COPD

2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
Takahito Chiba ◽  
Junichi Chihara ◽  
Masutaka Furue
Keyword(s):  
Inflammatory Diseases ◽  
Environmental Pollutants ◽  
Chronic Obstructive ◽  
Peroxisome Proliferator ◽  
Environmental Toxicants ◽  
Obstructive Pulmonary Disease ◽  
Mucin Production ◽  
Arylhydrocarbon Receptor ◽  
Peroxisome Proliferator Activated Receptors

The dioxins and dioxin-like compounds in cigarette smoke and environmental pollutants modulate immunological responses. These environmental toxicants are known to cause lung cancer but have also recently been implicated in allergic and inflammatory diseases such as bronchitis, asthma, and chronic obstructive pulmonary disease (COPD). In a novel pathway of this response, the activation of a nuclear receptor, arylhydrocarbon receptor (AhR), mediates the effects of these toxins through the arachidonic acid cascade, cell differentiation, cell-cell adhesion interactions, cytokine expression, and mucin production that are implicated in the pathogenesis and exacerbation of asthma/COPD. We have previously reported that human bronchial epithelial cells express AhR, and AhR activation induces mucin production through reactive oxygen species. This review discusses the role of AhR in asthma and COPD, focusing in particular on inflammatory and resident cells in the lung. We describe the important impact that AhR activation may have on the inflammation phase in the pathology of asthma and COPD. In addition, crosstalk of AhR signaling with other ligand-activated transcription factors such as peroxisome proliferator-activated receptors (PPARs) has been well documented.

scholarly journals The role of noncoding RNAs in regulating epithelial responses in COPD

2018 ◽  
Vol 315 (2) ◽  
pp. L184-L192 ◽  
Author(s):  
Yifan Chen ◽  
Paul S. Thomas ◽  
Rakesh K. Kumar ◽  
Cristan Herbert
Keyword(s):  
Inflammatory Responses ◽  
Noncoding Rnas ◽  
Chronic Inflammatory Disease ◽  
Airway Epithelial Cells ◽  
Chronic Obstructive ◽  
Airway Epithelial ◽  
Obstructive Pulmonary Disease ◽  
Regulatory Effects

Chronic obstructive pulmonary disease (COPD), one of the leading causes of death in the world, is a chronic inflammatory disease of the airways usually caused by long-term exposure to inhaled irritants. Airway epithelial cells (AECs) play a key role in initializing COPD and driving the exacerbation of this disease through the release of various cytokines. This AEC-derived cytokine response is tightly regulated possibly through the regulatory effects of noncoding RNAs (ncRNAs). Although the importance of ncRNAs in pulmonary diseases has been increasingly realized, little is known about the role of ncRNA in the regulation of inflammatory responses in COPD. This review outlines the features of AEC-derived cytokine responses in COPD and how ncRNAs regulate these inflammatory responses.

scholarly journals Clinical significance of changes in serum inflammatory factors in patients with chronic obstructive pulmonary disease and pulmonary infection

2021 ◽  
Vol 49 (5) ◽  
pp. 030006052110132
Author(s):  
Jun Zhou ◽  
Feng Jin ◽  
Feng Wu
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Lung Function ◽  
Pulmonary Disease ◽  
Pulmonary Infection ◽  
Inflammatory Responses ◽  
White Blood Cells ◽  
Inflammatory Factors ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Tnf Α

Background Chronic obstructive pulmonary disease (COPD) is often accompanied by pulmonary infection, inflammatory responses, decreased immunity, and decreased lung function. The relationships among the pulmonary inflammation index (PII), lung function, and immunity in COPD patients with pulmonary infection remain unclear. Methods This retrospective observational study enrolled 234 participants (patients with COPD and pulmonary infection, patients with COPD without pulmonary infection, and healthy individuals) from January 2017 to December 2019. Results Levels of interleukin (IL)-6 were lower and levels of IL-8 were higher in patients with COPD and pulmonary infection. Levels of white blood cells (WBCs), C-reactive protein (CRP), IL-6, IL-8, tumor necrosis factor (TNF)-α and CD8+ cells were higher, while levels of CD3+ and CD4+ cells, the CD4+/CD8+ ratio, forced expiratory volume in 1 s (FEV1), FEV1 % predicted (FEV1%pred), and FEV1/forced vital capacity (FVC) (FEV1%FVC) were lower in patients with COPD and pulmonary infection. Levels of WBCs, CRP, IL-6, IL-8, and TNF-α were negatively associated with FEV1, FEV1%pred and FEV1%FVC. Conclusions Patients with COPD and pulmonary infection have high PIIs, decreased immunity, and poor lung function. PII is closely related to lung function and may represent a useful biomarker for the assessment of patients with COPD and pulmonary infection.

scholarly journals Role of Apoptosis in Amplifying Inflammatory Responses in Lung Diseases

2010 ◽  
Vol 3 ◽  
pp. JCD.S5375 ◽  
Author(s):  
E.P. Schmidt ◽  
R.M. Tuder
Keyword(s):  
Lung Diseases ◽  
Inflammatory Responses ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Disease States ◽  
Chronic Lung Diseases ◽  
Cellular Environment ◽  
Molecular Patterns ◽  
Dying Cells

Apoptosis is an important contributor to the pathophysiology of lung diseases such as acute lung injury (ALI) and chronic obstructive pulmonary disease (COPD). Furthermore, the cellular environment of these acute and chronic lung diseases favors the delayed clearance of apoptotic cells. This dysfunctional efferocytosis predisposes to the release of endogenous ligands from dying cells. These so-called damage-associated molecular patterns (DAMPs) play an important role in the stimulation of innate immunity as well as in the induction of adaptive immunity, potentially against autoantigens. In this review, we explore the role of apoptosis in ALI and COPD, with particular attention to the contribution of DAMP release in augmenting the inflammatory response in these disease states.

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