Autophagy in immunity

Zhou, Xu‐jie; Zhang, Hong

doi:10.4161/auto.21212

Cited by 117 publications

(56 citation statements)

References 223 publications

(271 reference statements)

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“…Autophagy has been implicated in the pathogenesis of many diseases including cancer, neuro degenerative, cardiovascular, pulmonary, and autoimmune diseases [23,24]. Although pharmacologic modulation of autophagy has shown some early promises, current therapeutic targeting of autophagy is limited by an incomplete understanding of how autophagy contributes to pathogenesis [23].…”

Section: Discussionmentioning

confidence: 99%

Cyclic Mechanical Stretching Induces Autophagic Cell Death in Tenofibroblasts Through Activation of Prostaglandin E2 Production

Chen

Cheng

et al. 2015

Cell Physiol Biochem

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Background/Aims: Autophagic cell death has recently been implicated in the pathophysiology of tendinopathy. Prostaglandin E2 (PGE2), a known inflammatory mediator of tendinitis, inhibits tenofibroblast proliferation in vitro; however, the underlying mechanism is unclear. The present study investigated the relationship between PGE2 production and autophagic cell death in mechanically loaded human patellar tendon fibroblasts (HPTFs) in vitro. Methods: Cultured HPTFs were subjected to exogenous PGE2 treatment or repetitive cyclic mechanical stretching. Cell death was determined by flow cytometry with acridine orange/ethidium bromide staining. Induction of autophagy was assessed by autophagy markers including the formation of autophagosomes and autolysosomes (by electron microscopy, AO staining, and formation of GPF-LC3-labeled vacuoles) and the expression of LC3-II and BECN1 (by western blot). Stretching-induced PGE2 release was determined by ELISA. Results: Exogenous PGE2 significantly induced cell death and autophagy in HPTFs in a dose-dependent manner. Blocking autophagy using inhibitors 3-methyladenine and chloroquine, or small interfering RNAs against autophagy genes Becn-1 and Atg-5 prevented PGE2-induced cell death. Cyclic mechanical stretching at 8% and 12% magnitudes for 24 h significantly stimulated PGE2 release by HPTFs in a magnitude-dependent manner. In addition, mechanical stretching induced autophagy and cell death. Blocking PGE2 production using COX inhibitors indomethacin and celecoxib significantly reduced stretching-induced autophagy and cell death. Conclusion: Taken together, cyclic mechanical stretching induces autophagic cell death in tenofibroblasts through activation of PGE2 production.

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Section: Discussionmentioning

confidence: 99%

Cyclic Mechanical Stretching Induces Autophagic Cell Death in Tenofibroblasts Through Activation of Prostaglandin E2 Production

Chen

Cheng

et al. 2015

Cell Physiol Biochem

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“…Genome-wide association studies have linked nucleotide polymorphisms in autophagy-related genes to susceptibility for SLE [29–31]. At least five single nucleotide polymorphisms (SNPs) near to and in the Atg5 locus are associated with SLE initiation and/or development.…”

Section: Autophagy In Autoimmune Diseasementioning

confidence: 99%

“…According to Zhou et.al. , SNPs within the intragenic region of PRDM1-Atg5 are also associated with SLE in the Chinese population [31]. It is currently unknown how SNPs within intragenic regions regulate gene expression of Atg5 and an integrated mechanism for Atg5 in the development of SLE has not been defined.…”

Section: Autophagy In Autoimmune Diseasementioning

confidence: 99%

Autophagy in autoimmune disease

2015

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Autophagy is a protective and life-sustaining process in which cytoplasmic components are packaged into double-membrane vesicles and targeted to lysosomes for degradation. This process of cellular self-digestion is an essential stress response and is cytoprotective by removing damaged organelles and proteins that threaten the cell’s survival. Key outcomes include energy generation and recycling of metabolic precursors. In the immune system, autophagy regulates processes such as antigen uptake and presentation, removal of pathogens, survival of short- and long-lived immune cells and cytokine-dependent inflammation. In all cases, a window of optimal autophagic activity appears critical to balance catabolic, reparative and inflammation-inducing processes. Dysregulation of autophagosome formation and autophagic flux can have deleterious consequences, ranging from a failure to “clean house” to the induction of autophagy-induced cell death. Abnormalities in the autophagic pathway have been implicated in numerous autoimmune diseases. Genome-wide association studies have linked polymorphisms in autophagy-related genes with predisposition for tissue-destructive inflammatory disease, specifically in inflammatory bowel disease and systemic lupus erythematosus. Although the precise mechanisms by which dysfunctional autophagy renders the host susceptible to continuous inflammation remain unclear, autophagy’s role in regulating the long-term survival of adaptive immune cells has recently surfaced as a defect in multiple sclerosis and rheumatoid arthritis. Efforts are underway to identify autophagy-inducing and autophagy-suppressing pharmacologic interventions that can be added to immunosuppressive therapy to improve outcomes of patients with autoimmune disease.

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“…Macroautophagy is thought to be the major type of autophagy and it has been studied most extensively compared to microautophagy and chaperone-mediated autophagy [46]. Autophagy can be upregulated in response to extra or intracellular stress and signals such as starvation, growth factor deprivation, endoplasmic reticulum (ER) stress, accumulation of unfolded proteins, and infection [48]. One of the best characterized substrates of selective autophagy is p62, which is also known as sequestosome 1/SQSTM1.…”

Section: Oxidative Stress and Autophagymentioning

confidence: 99%

Dysfunction of Autophagy: A Possible Mechanism Involved in the Pathogenesis of Vitiligo by Breaking the Redox Balance of Melanocytes

Qiao

Wang

Xiang

et al. 2016

Oxidative Medicine and Cellular Longevity

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Vitiligo is a common chronic acquired pigmentation disorder characterized by loss of functional melanocytes from the epidermis and follicular reservoir. Among multiple hypotheses which have been proposed in the pathogenesis of vitiligo, autoimmunity and oxidative stress-mediated toxicity in melanocytes remain most widely accepted. Macroautophagy is a lysosome-dependent degradation pathway which widely exists in eukaryotic cells. Autophagy participates in the oxidative stress response in many cells, which plays a protective role in preventing damage caused by oxidative stress. Recent studies have enrolled autophagy as an important regulator in limiting damage caused by UV light and lipid oxidation, keeping oxidative stress in a steady state in epidermal keratinocytes and maintaining normal proliferation and aging of melanocytes. Impairment of autophagy might disrupt the antioxidant defense system which renders melanocytes to oxidative insults. These findings provide supportive evidence to explore new ideas of the pathogenesis of vitiligo and other pigmentation disorders.

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Autophagy in immunity

Cited by 117 publications

References 223 publications

Cyclic Mechanical Stretching Induces Autophagic Cell Death in Tenofibroblasts Through Activation of Prostaglandin E2 Production

Cyclic Mechanical Stretching Induces Autophagic Cell Death in Tenofibroblasts Through Activation of Prostaglandin E2 Production

Autophagy in autoimmune disease

Dysfunction of Autophagy: A Possible Mechanism Involved in the Pathogenesis of Vitiligo by Breaking the Redox Balance of Melanocytes

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