Inhibition of thymocyte autophagy-associated CD4+T thymopoiesis is involved in asthma susceptibility in mice exposed to caffeine prenatally

Liu, Hanxiao; Yan, Hui-yi; Qu, Wen; Wen, Xiaoru; Hou, Lifang; Zhao, Wenzhi; Ping, Jie

doi:10.1007/s00204-019-02418-5

Cited by 11 publications

(8 citation statements)

References 45 publications

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“…Therefore, caffeine also has the potential in protection of skin disease. Consistent with these studies, a recent research found that caffeine directly enhanced autophagy in concentration-and timedependent manners in primary cultured thymocytes, which was dependent on A 2A R signaling (Liu et al, 2019). Taken together, these studies from various cell models and in different tissues and organs in vivo demonstrate that caffeine enhances autophagy which is related to its therapeutic effects on diverse human diseases, including tumors, aging, liver fibrosis, and skin disease.…”

Section: Caffeine May Modulate Pd Pathology By Regulating Autophagy Asupporting

confidence: 68%

Caffeine and Parkinson’s Disease: Multiple Benefits and Emerging Mechanisms

2020

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Parkinson’s disease (PD) is the second most common neurodegenerative disorder, characterized by dopaminergic neurodegeneration, motor impairment and non-motor symptoms. Epidemiological and experimental investigations into potential risk factors have firmly established that dietary factor caffeine, the most-widely consumed psychoactive substance, may exerts not only neuroprotective but a motor and non-motor (cognitive) benefits in PD. These multi-benefits of caffeine in PD are supported by convergence of epidemiological and animal evidence. At least six large prospective epidemiological studies have firmly established a relationship between increased caffeine consumption and decreased risk of developing PD. In addition, animal studies have also demonstrated that caffeine confers neuroprotection against dopaminergic neurodegeneration using PD models of mitochondrial toxins (MPTP, 6-OHDA, and rotenone) and expression of α-synuclein (α-Syn). While caffeine has complex pharmacological profiles, studies with genetic knockout mice have clearly revealed that caffeine’s action is largely mediated by the brain adenosine A2A receptor (A2AR) and confer neuroprotection by modulating neuroinflammation and excitotoxicity and mitochondrial function. Interestingly, recent studies have highlighted emerging new mechanisms including caffeine modulation of α-Syn degradation with enhanced autophagy and caffeine modulation of gut microbiota and gut-brain axis in PD models. Importantly, since the first clinical trial in 2003, United States FDA has finally approved clinical use of the A2AR antagonist istradefylline for the treatment of PD with OFF-time in Sept. 2019. To realize therapeutic potential of caffeine in PD, genetic study of caffeine and risk genes in human population may identify useful pharmacogenetic markers for predicting individual responses to caffeine in PD clinical trials and thus offer a unique opportunity for “personalized medicine” in PD.

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Section: Caffeine May Modulate Pd Pathology By Regulating Autophagy Asupporting

confidence: 68%

Caffeine and Parkinson’s Disease: Multiple Benefits and Emerging Mechanisms

2020

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“…This process relies on the reprogramming of monocyte inflammatory response mediated by ARG transcription factor EB and is related to the severity of asthma ( 46 ). However, the specific role of autophagy in asthma is still controversial ( 47 , 48 ). For example, neutrophils can increase the level of airway inflammation in severe asthma by destroying airway epithelial cells through autophagy ( 11 ), but the conditional knockout of ATG5 and lack of autophagy can induce neutrophil-infiltrated airway inflammation and AHR, further leading to hormone-resistant asthma ( 13 ).…”

Section: Discussionmentioning

confidence: 99%

Autophagy-Related Genes Are Involved in the Progression and Prognosis of Asthma and Regulate the Immune Microenvironment

et al. 2022

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BackgroundAutophagy has been proven to play an important role in the pathogenesis of asthma and the regulation of the airway epithelial immune microenvironment. However, a systematic analysis of the clinical importance of autophagy-related genes (ARGs) regulating the immune microenvironment in patients with asthma remains lacking.MethodsClustering based on the k-means unsupervised clustering method was performed to identify autophagy-related subtypes in asthma. ARG-related diagnostic markers in low-autophagy subtypes were screened, the infiltration of immune cells in the airway epithelium was evaluated by the CIBERSORT, and the correlation between diagnostic markers and infiltrating immune cells was analyzed. On the basis of the expression of ARGs and combined with asthma control, a risk prediction model was established and verified by experiments.ResultsA total of 66 differentially expressed ARGs and 2 subtypes were identified between mild to moderate and severe asthma. Significant differences were observed in asthma control and FEV1 reversibility between the two subtypes, and the low-autophagy subtype was closely associated with severe asthma, energy metabolism, and hormone metabolism. The autophagy gene SERPINB10 was identified as a diagnostic marker and was related to the infiltration of immune cells, such as activated mast cells and neutrophils. Combined with asthma control, a risk prediction model was constructed, the expression of five risk genes was supported by animal experiments, was established for ARGs related to the prediction model.ConclusionAutophagy plays a crucial role in the diversity and complexity of the asthma immune microenvironment and has clinical value in treatment response and prognosis.

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“…It has been shown that PM 2.5 exposure can induce cell autophagy and airway inflammation through different immunological and molecular mechanisms (44–46). Furthermore, exposure to allergens has also been shown to activate autophagy, as demonstrated in studies with cockroach allergen (47), Alternaria extract (48), and caffeine (49).…”

Section: Autophagymentioning

confidence: 98%

Environmental Exposures and Asthma Development: Autophagy, Mitophagy, and Cellular Senescence

et al. 2019

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Environmental pollutants and allergens induce oxidative stress and mitochondrial dysfunction, leading to key features of allergic asthma. Dysregulations in autophagy, mitophagy, and cellular senescence have been associated with environmental pollutant and allergen-induced oxidative stress, mitochondrial dysfunction, secretion of multiple inflammatory proteins, and subsequently development of asthma. Particularly, particulate matter 2.5 (PM2.5) has been reported to induce autophagy in the bronchial epithelial cells through activation of AMP-activated protein kinase (AMPK), drive mitophagy through activating PTEN-induced kinase 1(PINK1)/Parkin pathway, and induce cell cycle arrest and senescence. Intriguingly, allergens, including ovalbumin (OVA), Alternaria alternata, and cockroach allergen, have also been shown to induce autophagy through activation of different signaling pathways. Additionally, mitochondrial dysfunction can induce cell senescence due to excessive ROS production, which affects airway diseases. Although autophagy and senescence share similar properties, recent studies suggest that autophagy can either accelerate the development of senescence or prevent senescence. Thus, in this review, we evaluated the literature regarding the basic cellular processes, including autophagy, mitophagy, and cellular senescence, explored their molecular mechanisms in the regulation of the initiation and downstream signaling. Especially, we highlighted their involvement in environmental pollutant/allergen-induced major phenotypic changes of asthma such as airway inflammation and remodeling and reviewed novel and critical research areas for future studies. Ultimately, understanding the regulatory mechanisms of autophagy, mitophagy, and cellular senescence may allow for the development of new therapeutic targets for asthma.

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Inhibition of thymocyte autophagy-associated CD4+T thymopoiesis is involved in asthma susceptibility in mice exposed to caffeine prenatally

Cited by 11 publications

References 45 publications

Caffeine and Parkinson’s Disease: Multiple Benefits and Emerging Mechanisms

Caffeine and Parkinson’s Disease: Multiple Benefits and Emerging Mechanisms

Autophagy-Related Genes Are Involved in the Progression and Prognosis of Asthma and Regulate the Immune Microenvironment

Environmental Exposures and Asthma Development: Autophagy, Mitophagy, and Cellular Senescence

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