Suppression of sirtuin 1 alleviates airway inflammation through mTOR‑mediated autophagy

Wu, Yuanyuan; Li, Wei; Hu, Yifan; Liu, Yun; Sun, Xuegang

doi:10.3892/mmr.2020.11338

Cited by 17 publications

(15 citation statements)

References 33 publications

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“…Interestingly, other studies demonstrated that knockdown of Mtor in airway epithelial cells resulted in increased recruitment of inflammatory cells and eosinophils in the BAL, enhanced mucus accumulation, exacerbated AHR and heightened IL-25 levels, following HDM and/or OVA challenge (Table 1, Supplementary Figure S1) [146]. In support, the administration of EX-527, a SIRT1 inhibitor, suppressed airway inflammation and reduced IL-4, IL-13, and IFN-γ levels in the BAL, associated with enhanced mTOR activation and decreased autophagy induction, effects that were reversed by concomitant rapamycin treatment [147]. Further support of a pathogenic role for autophagy in AAI came from studies in Atg16l1-deficient mice which exhibited attenuated mucus secretion upon intranasal IL-33 administration [75].…”

Section: Role Of Autophagy In Allergic Airway Inflammation In Vivomentioning

confidence: 79%

Autophagy: A Friend or Foe in Allergic Asthma?

Theofani

Xanthou

2021

IJMS

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Autophagy is a major self-degradative process through which cytoplasmic material, including damaged organelles and proteins, are delivered and degraded in the lysosome. Autophagy represents a dynamic recycling system that produces new building blocks and energy, essential for cellular renovation, physiology, and homeostasis. Principal autophagy triggers include starvation, pathogens, and stress. Autophagy plays also a pivotal role in immune response regulation, including immune cell differentiation, antigen presentation and the generation of T effector responses, the development of protective immunity against pathogens, and the coordination of immunometabolic signals. A plethora of studies propose that both impaired and overactive autophagic processes contribute to the pathogenesis of human disorders, including infections, cancer, atherosclerosis, autoimmune and neurodegenerative diseases. Autophagy has been also implicated in the development and progression of allergen-driven airway inflammation and remodeling. Here, we provide an overview of recent studies pertinent to the biology of autophagy and molecular pathways controlling its activation, we discuss autophagy-mediated beneficial and detrimental effects in animal models of allergic diseases and illuminate new advances on the role of autophagy in the pathogenesis of human asthma. We conclude contemplating the potential of targeting autophagy as a novel therapeutic approach for the management of allergic responses and linked asthmatic disease.

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Section: Role Of Autophagy In Allergic Airway Inflammation In Vivomentioning

confidence: 79%

Autophagy: A Friend or Foe in Allergic Asthma?

Theofani

Xanthou

2021

IJMS

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“…Other SIRT1-related pathways also play an important role in regulating respiratory diseases, and the mechanisms may involve influencing autophagy, anti-inflammation, anti-apoptosis, and so on ( 55 56 57 58 59 ). Recent reports have shown that regulating SIRT1/NF-κB pathway can inhibit TNF-α-induced pro-inflammatory responses ( 60 ).…”

Section: Downstream Pathways and Mechanisms Through Hmgb1mentioning

confidence: 99%

As a Modulator, Multitasking Roles of SIRT1 in Respiratory Diseases

2022

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As far the current severe coronavirus disease 2019 (COVID-19), respiratory disease is still the biggest threat to human health. In addition, infectious respiratory diseases are particularly prominent. In addition to killing and clearing the infection pathogen directly, regulating the immune responses against the pathogens is also an important therapeutic modality. Sirtuins belong to NAD+-dependent class III histone deacetylases. Among 7 types of sirtuins, silent information regulator type-1 (SIRT1) played a multitasking role in modulating a wide range of physiological processes, including oxidative stress, inflammation, cell apoptosis, autophagy, antibacterial and antiviral functions. It showed a critical effect in regulating immune responses by deacetylation modification, especially through high-mobility group box 1 (HMGB1), a core molecule regulating the immune system. SIRT1 was associated with many respiratory diseases, including COVID-19 infection, bacterial pneumonia, tuberculosis, and so on. Here, we reviewed the latest research progress regarding the effects of SIRT1 on immune system in respiratory diseases. First, the structure and catalytic characteristics of SIRT1 were introduced. Next, the roles of SIRT1, and the mechanisms underlying the immune regulatory effect through HMGB1, as well as the specific activators/inhibitors of SIRT1, were elaborated. Finally, the multitasking roles of SIRT1 in several respiratory diseases were discussed separately. Taken together, this review implied that SIRT1 could serve as a promising specific therapeutic target for the treatment of respiratory diseases.

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“…We identified SIRT1 as a direct target of miR-9 ( Figure 5A ). SIRT1 is necessary for mast cell signaling and anaphylaxis ( Li et al, 2018 ), and mediates allergic airway inflammation via autophagy ( Wu et al, 2020 ). SIRT1/NF-kB/TLR2 signaling promotes inflammatory responses in macrophages ( Qian et al, 2018 ).…”

Section: Discussionmentioning

confidence: 99%

“…SIRT1/nuclear factor-κB (NF-κB) signaling is necessary for allergic rhinitis ( Niu et al, 2020 ). SIRT1 contributes to the pathogenesis of asthma by promoting autophagy ( Wu et al, 2020 ). While an increased expression of SIRT1 has been reported in a murine model of AD ( Lee et al, 2020 ), the role of SIRT1 in AD have not been studied in sufficient detail.…”

Section: Introductionmentioning

confidence: 99%

HDAC6 and CXCL13 Mediate Atopic Dermatitis by Regulating Cellular Interactions and Expression Levels of miR-9 and SIRT1

et al. 2021

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Histone deacetylase 6 (HDAC6) has been known to regulate inflammatory diseases. The role of HDAC6 in allergic skin inflammation has not been studied. We studied the role of HDAC6 in atopic dermatitis (AD) and the mechanisms associated with it. The decreased expression or chemical inhibition of HDAC6 suppressed AD by decreasing autophagic flux and cellular features of AD. AD increased expression levels of the Th1 and Th2 cytokines, but decreased expression levels of forkhead box P3 (FoxP3) and interleukin-10 (IL-10) in an HDAC6-dependent manner. CXC chemokine ligand 13 (CXCL13), which was increased in an HDAC6-depenednt manner, mediated AD. MiR-9, negatively regulated by HDAC6, suppressed AD by directly regulating the expression of sirtuin 1 (SIRT1). The downregulation or inhibition of SIRT1 suppressed AD. Experiments employing culture medium and transwell suggested that cellular interactions involving mast cells, keratinocytes, and dermal fibroblast cells could promote AD; HDAC6 and CXCL13 were found to be necessary for these cellular interactions. Mouse recombinant CXCL13 protein increased HDAC6 expression in skin mast cells and dermal fibroblast cells. CXCL13 protein was found to be present in the exosomes of DNCB-treated skin mast cells. Exosomes of DNCB-treated skin mast cells enhanced invasion potentials of keratinocytes and dermal fibroblast cells and increased expression levels of HDAC6, SIRT1 and CXCL13 in keratinocytes and dermal fibroblast cells. These results indicate that HDAC6 and CXCL13 may serve as targets for the developing anti-atopic drugs.

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Suppression of sirtuin 1 alleviates airway inflammation through mTOR‑mediated autophagy

Cited by 17 publications

References 33 publications

Autophagy: A Friend or Foe in Allergic Asthma?

Autophagy: A Friend or Foe in Allergic Asthma?

As a Modulator, Multitasking Roles of SIRT1 in Respiratory Diseases

HDAC6 and CXCL13 Mediate Atopic Dermatitis by Regulating Cellular Interactions and Expression Levels of miR-9 and SIRT1

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