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Inhibition of glutaminase 1 activity reverses airway hyperresponsiveness and decreases IL-1β+ M1s and IL-17 producing ILC3s in high-fat diet-fed obese mice
- Title
- Inhibition of glutaminase 1 activity reverses airway hyperresponsiveness and decreases IL-1β+ M1s and IL-17 producing ILC3s in high-fat diet-fed obese mice
- Authors
- Shim J.-S.; Lee H.-S.; Kwon H.; Kim M.-H.; Cho Y.-J.; Park H.-W.
- Ewha Authors
- 조영주; 김민혜; 심지수
- SCOPUS Author ID
- 조영주; 김민혜; 심지수
- Issue Date
- 2023
- Journal Title
- American Journal of Physiology - Lung Cellular and Molecular Physiology
- ISSN
- 1040-0605
- Citation
- American Journal of Physiology - Lung Cellular and Molecular Physiology vol. 324, no. 5, pp. L625 - L638
- Keywords
- asthma; glutamine; innate lymphoid cells; macrophages; obesity
- Publisher
- American Physiological Society
- Indexed
- SCIE; SCOPUS
- Document Type
- Article
- Abstract
- In obesity, disturbed glutamine metabolism contributes to enhanced inflammation by inducing alterations in immune cells. As macrophages and innate lymphoid cells (ILCs) are known to be involved in the pathogenesis of obesity-related asthma, we tested our hypothesis that altered glutamine metabolism may link obesity to airway hyperresponsivenss (AHR), a cardinal feature of asthma, focusing on these innate immune cells. Four-week-old male C57BL/6 mice were fed a high-fat diet (HFD) for 13 wk in the presence or absence of BPTES [Bis-2-(5-phenylacetamido-1,3,4-thiadiazol-2-yl)ethyl sulfide, a selective inhibitor of glutaminase 1 which converts glutamine to glutamate] and their blood, lung, and adipose tissues were analyzed. We then conducted in vitro experiments using bone marrow-derived macrophages (BMDMs) and mouse alveolar macrophage cell line. Furthermore, we investigated plasma glutamine and glutamate levels in obese and nonobese asthmatics. BPTES treatment prevented HFD-induced AHR and significantly decreased IL-1β+ classically activated macrophages (M1s) and type 3 ILCs (ILC3s) which increased in the lungs of HFD-fed obese mice. In in vitro experiments, BPTES treatment or glutamine supplement significantly reduced the proportion of IL-1β+NLRP3+ M1s in lipopolysaccharide-stimulated BMDMs and mouse alveolar macrophage cell line. BPTES treatment also significantly reduced the IL-17 producing ILC3s differentiated from ILCs in naïve mouse lung. In addition, plasma glutamate/glutamine ratios were significantly higher in obese asthmatics compared to nonobese asthmatics. Inhibition of glutaminolysis reverses AHR in HFD-induced obese mice and decreases IL-1β + NLRP3+ M1s and IL-17 producing ILC3s, which suggests altered glutamine metabolism may have a role in the pathogenesis of obesity-related AHR. Copyright © 2023 the American Physiological Society.
- DOI
- 10.1152/ajplung.00181.2022
- Appears in Collections:
- 의과대학 > 의학과 > Journal papers
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