Autophagy in chronic lung disease

Racanelli, Alexandra C.; Choi, Augustine M.K.; Choi, Mary E.

doi:10.1016/bs.pmbts.2020.02.001

Cited by 22 publications

(18 citation statements)

References 103 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…It is suggested that STING then traffics to lysosomes, where it is degraded [38]. Since a role for autophagy has been described in lung pathology [39], understanding how STING gain-of-function can perturbate autophagy biology in lungs would be relevant for the comprehension of pulmonary disease in SAVI.…”

Section: Sting and Autophagymentioning

confidence: 99%

Lung Inflammation in STING-Associated Vasculopathy with Onset in Infancy (SAVI)

David

Frémond

2022

Cells

View full text Add to dashboard Cite

STING-associated vasculopathy with onset in infancy (SAVI) is a type I interferonopathy caused by gain-of-function mutations in STING1 encoding stimulator of interferon genes (STING) protein. SAVI is characterized by severe inflammatory lung disease, a feature not observed in previously described type I interferonopathies i.e., Mendelian autoinflammatory disorders defined by constitutive activation of the type I interferon (IFN) pathway. Molecular defects in nucleic acid metabolism or sensing are central to the pathophysiology of these diseases, with such defects occurring at any step of the tightly regulated pathway of type I IFN production and signaling (e.g., exonuclease loss of function, RNA-DNA hybrid accumulation, constitutive activation of adaptor proteins such as STING). Among over 30 genotypes, SAVI and COPA syndrome, whose pathophysiology was recently linked to a constitutive activation of STING signaling, are the only type I interferonopathies presenting with predominant lung involvement. Lung disease is the leading cause of morbidity and mortality in these two disorders which do not respond to conventional immunosuppressive therapies and only partially to JAK1/2 inhibitors. In human silicosis, STING-dependent sensing of self-DNA following cell death triggered by silica exposure has been found to drive lung inflammation in mice and human models. These recent findings support a key role for STING and nucleic acid sensing in the homeostasis of intrinsic pulmonary inflammation. However, mechanisms by which monogenic defects in the STING pathway lead to pulmonary damages are not yet fully elucidated, and an improved understanding of such mechanisms is fundamental to improved future patient management. Here, we review the recent insights into the pathophysiology of SAVI and outline our current understanding of self-nucleic acid-mediated lung inflammation in humans.

show abstract

Section: Sting and Autophagymentioning

confidence: 99%

Lung Inflammation in STING-Associated Vasculopathy with Onset in Infancy (SAVI)

David

Frémond

2022

Cells

View full text Add to dashboard Cite

show abstract

“…The primary targets of inhaled CS are airway and alveolar epithelial cells (Racanelli et al, 2018). Exposure to CS, uncontrolled chronic inflammation and oxidative stress are the main drivers of the pathogenesis of COPD in airway epithelial cells, and are involved in many forms of regulated cell death (i.e., apoptosis, necroptosis, and autophagy) (Racanelli et al, 2020). Smoking is a major cause of systemic oxidative stress, excessive inflammation, and emphysema.…”

Section: Regulation Of Autophagy During Oxidative Stress In Copd Copd...mentioning

confidence: 99%

The interplay between oxidative stress and autophagy in chronic obstructive pulmonary disease

2022

View full text Add to dashboard Cite

Autophagy is a highly conserved process that is indispensable for cell survival, embryonic development, and tissue homeostasis. Activation of autophagy protects cells against oxidative stress and is a major adaptive response to injury. When autophagy is dysregulated by factors such as smoking, environmental insults and aging, it can lead to enhanced formation of aggressors and production of reactive oxygen species (ROS), resulting in oxidative stress and oxidative damage to cells. ROS activates autophagy, which in turn promotes cell adaptation and reduces oxidative damage by degrading and circulating damaged macromolecules and dysfunctional cell organelles. The cellular response triggered by oxidative stress includes changes in signaling pathways that ultimately regulate autophagy. Chronic obstructive pulmonary disease (COPD) is the most common lung disease among the elderly worldwide, with a high mortality rate. As an induced response to oxidative stress, autophagy plays an important role in the pathogenesis of COPD. This review discusses the regulation of oxidative stress and autophagy in COPD, and aims to provide new avenues for future research on target-specific treatments for COPD.

show abstract

“…Abnormal autophagy plays a critical role in the pathogenesis of many diseases, including cancer, neurodegenerative diseases, atherosclerosis and chronic inflammatory diseases [ 5 ]. There is increasing evidence that autophagy also plays an important role in several chronic lung diseases and may be a target for new therapies [ 6 ]. Here we review the role of macroautophagy in asthma and chronic constructive pulmonary disease (COPD), which are the most prevalent lung diseases.…”

Section: Introductionmentioning

confidence: 99%

Autophagy in asthma and chronic obstructive pulmonary disease

2022

View full text Add to dashboard Cite

Autophagy (or macroautophagy) is a key cellular process that removes damaged molecules (particularly proteins) and subcellular organelles to maintain cellular homeostasis. There is growing evidence that abnormalities in autophagy may contribute to the pathogenesis of many chronic diseases, including asthma and chronic obstructive pulmonary disease (COPD). In asthma, increased autophagy plays a role in promoting type 2 immune responses and eosinophilic inflammation, whereas decreased autophagy may be important in neutrophilic asthma. Acute exposure to cigarette smoke may activate autophagy, resulting in ciliary dysfunction and death of airway epithelial cells, whereas in stable COPD most studies have demonstrated an impairment in autophagy, with reduced autophagic flux and accumulation of abnormal mitochondria (defective mitophagy) and linked to cellular senescence. Autophagy may be increased or decreased in different cell types and depending on the cellular environment, making it difficult to target autophagy therapeutically. Several existing drugs may activate autophagy, including rapamycin, metformin, carbamazepine, cardiac glycosides and statins, whereas others, such as chloroquine, inhibit this process. However, these drugs are nonspecific and more selective drugs are now in development, which may prove useful as novel agents to treat asthma and COPD in the future.

show abstract

Autophagy in chronic lung disease

Cited by 22 publications

References 103 publications

Lung Inflammation in STING-Associated Vasculopathy with Onset in Infancy (SAVI)

Lung Inflammation in STING-Associated Vasculopathy with Onset in Infancy (SAVI)

The interplay between oxidative stress and autophagy in chronic obstructive pulmonary disease

Autophagy in asthma and chronic obstructive pulmonary disease

Contact Info

Product

Resources

About