Autophagy and Asthma

Farooq, M.; Walsh, Garry Michael

doi:10.1111/cea.12633

Cited by 14 publications

(8 citation statements)

References 22 publications

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“…Previous studies have reported that mTOR signaling is involved in inflammatory diseases, including dermatological ailments ( 13 ), chronic obstructive pulmonary disease ( 14 , 15 ) and asthma ( 16 ). Furthermore, it was revealed that autophagy may be involved in the regulation of asthma ( 17 , 18 ), and enhanced autophagy was reported to be associated with increased asthma severity ( 18 ). Autophagy is controlled by the mTOR signaling pathway ( 19 ).…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2020

Mol Med Rep

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Sirtuin 1 (SirT1) is involved in the pathogenesis of allergic asthma. This study aimed to investigate whether eX-527, a specific SirT1 inhibitor, exerted suppressive effects on allergic airway inflammation in mice submitted to ovalbumin (oVa) inhalation. in addition, this study assessed whether such a protective role was mediated by autophagy suppression though mammalian target of rapamycin (mTor) activation. Female c57Bl/6 mice were sensitized to oVa and eX-527 (10 mg/kg) was administered prior to oVa challenge. The study found that eX-527 reversed oVa-induced airway inflammation, and reduced OVA-induced increases in inflammatory cytokine expression, and total cell and eosinophil counts in bronchoalveolar lavage fluid. In addition, EX-527 enhanced mTor activation, thereby suppressing autophagy in allergic mice. To assess whether EX-527 inhibited airway inflammation in asthma through the mTor-mediated autophagy pathway, rapamycin was administered to mice treated with eX-527 after oVa sensitization. all effects induced by eX-527, including increased phosphorylated-mTor and decreased autophagy, were abrogated by rapamycin treatment. Taken together, the present findings indicated that EX-527 may inhibit allergic airway inflammation by suppressing autophagy, an effect mediated by mTor activation in allergic mice.

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Section: Introductionmentioning

confidence: 99%

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

et al. 2020

Mol Med Rep

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“…Asthma is a common chronic respiratory disease with significant morbidity and mortality around the world, which affects about 300 million people of all races and age groups [1]. Emerging evidence has highlighted the importance of autophagy in asthma [2][3][4][5][6]. Autophagy is an evolutionarily conserved cellular process for degrading unfolded or long-lived proteins, impaired cytoplasmic organelles, ROS (reactive oxygen species) and recycling amino acids in eukaryotic cells [7].…”

Section: Introductionmentioning

confidence: 99%

IL4 (interleukin 4) induces autophagy in B cells leading to exacerbated asthma

et al. 2018

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Allergic asthma is a common airway inflammatory disease in which B cells play important roles through IgE production and antigen presentation. SNP (single nucleotide polymorphism) analysis showed that Atg (autophagy-related) allele mutations are involved in asthma. It has been demonstrated that macroautophagy/autophagy is essential for B cell survival, plasma cell differentiation and immunological memory maintenance. However, whether B cell autophagy participates in asthma pathogenesis remains to be investigated. In this report, we found that autophagy was enhanced in pulmonary B cells from asthma-prone mice. Autophagy deficiency in B cells led to attenuated immunopathological symptoms in asthma-prone mice. Further investigation showed that IL4 (interleukin 4), a key effector Th2 cytokine in allergic asthma, was critical for autophagy induction in B cells both in vivo and in vitro, which further sustained B cell survival and enhanced antigen presentation by B cells. Moreover, IL4-induced autophagy depended on JAK signaling via an MTOR-independent, PtdIns3K-dependent pathway. Together, our data indicate that B cell autophagy aggravates experimental asthma through multiple mechanisms.

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“…Macrophage polarization is selectively regulated by the mTORC1-Akt-TSC1 loop 19 , and its regulatory role may be reversed when facing acute activation or chronic activation of mTORC1. In eosinophil-related research, the loss of mTOR can lead to autophagy activation, which has been observed in the peripheral blood eosinophils of severe asthma patients 20 , 21 . Therefore, this indicates that mTOR may contribute to asthmatic pathogenesis through regulation of eosinophil development or function.…”

Section: Introductionmentioning

confidence: 99%

mTOR complexes differentially orchestrates eosinophil development in allergy

Zhu

Xia

et al. 2018

Sci Rep

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Eosinophil infiltration is considered a hallmark in allergic airway inflammation, and the blockade of eosinophil differentiation may be an effective approach for treating eosinophil-related disorders. Mammalian target of rapamycin (mTOR) is a vital modulator in cell growth control and related diseases, and we have recently demonstrated that rapamycin can suppress eosinophil differentiation in allergic airway inflammation. Considering its critical role in haematopoiesis, we further investigated the role of mTOR in eosinophil differentiation in the context of asthmatic pathogenesis. Intriguingly, the inhibition of mTOR, either by genetic deletion or by another pharmacological inhibitor torin-1, accelerated the eosinophil development in the presence of IL-5. However, this was not observed to have any considerable effect on eosinophil apoptosis. The effect of mTOR in eosinophil differentiation was mediated by Erk signalling. Moreover, myeloid specific knockout of mTOR or Rheb further augmented allergic airway inflammation in mice after allergen exposure. Ablation of mTOR in myeloid cells also resulted in an increased number of eosinophil lineage-committed progenitors (Eops) in allergic mice. Collectively, our data uncovered the differential effects of mTOR in the regulation of eosinophil development, likely due to the distinct functions of mTOR complex 1 or 2, which thus exerts a pivotal implication in eosinophil-associated diseases.

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Autophagy and Asthma

Cited by 14 publications

References 22 publications

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

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

IL4 (interleukin 4) induces autophagy in B cells leading to exacerbated asthma

mTOR complexes differentially orchestrates eosinophil development in allergy

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