Inhibition of γ-glutamyl transferase suppresses airway hyperresponsiveness and airway inflammation in a mouse model of steroid resistant asthma exacerbation
IntroductionDespite recent advances, there are limited treatments available for acute asthma exacerbations. Here, we investigated the therapeutic potential of GGsTop, a γ-glutamyl transferase inhibitor, on the disease with a murine model of asthma exacerbation.MethodsGGsTop was administered to mice...
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Frontiers Media S.A.
2023-06-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1132939/full |
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| author | Cancan Zhang Huisha Xu Keilah G. Netto Leon A. Sokulsky Yiyan Miao Zhongyuan Mo Yan Meng Yingying Du Chengyong Wu Liyou Han Lirong Zhang Chi Liu Guojun Zhang Fuguang Li Ming Yang Ming Yang |
| author_facet | Cancan Zhang Huisha Xu Keilah G. Netto Leon A. Sokulsky Yiyan Miao Zhongyuan Mo Yan Meng Yingying Du Chengyong Wu Liyou Han Lirong Zhang Chi Liu Guojun Zhang Fuguang Li Ming Yang Ming Yang |
| author_sort | Cancan Zhang |
| collection | DOAJ |
| description | IntroductionDespite recent advances, there are limited treatments available for acute asthma exacerbations. Here, we investigated the therapeutic potential of GGsTop, a γ-glutamyl transferase inhibitor, on the disease with a murine model of asthma exacerbation.MethodsGGsTop was administered to mice that received lipopolysaccharide (LPS) and ovalbumin (OVA) challenges. Airway hyperresponsiveness (AHR), lung histology, mucus hypersecretion, and collagen deposition were analyzed to evaluate the hallmark features of asthma exacerbation. The level of proinflammatory cytokines and glutathione were determined with/without GGsTop. The transcription profiles were also examined.ResultsGGsTop attenuates hallmark features of the disease with a murine model of LPS and OVA driven asthma exacerbation. Airway hyperresponsiveness (AHR), mucus hypersecretion, collagen deposition, and expression of inflammatory cytokines were dramatically inhibited by GGsTop treatment. Additionally, GGsTop restored the level of glutathione. Using RNA-sequencing and pathway analysis, we demonstrated that the activation of LPS/NFκB signaling pathway in airway was downregulated by GGsTop. Interestingly, further analysis revealed that GGsTop significantly inhibited not only IFNγ responses but also the expression of glucocorticoid-associated molecules, implicating that GGsTop profoundly attenuates inflammatory pathways.ConclusionsOur study suggests that GGsTop is a viable treatment for asthma exacerbation by broadly inhibiting the activation of multiple inflammatory pathways. |
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| language | English |
| last_indexed | 2024-03-13T06:04:56Z |
| publishDate | 2023-06-01 |
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| series | Frontiers in Immunology |
| spelling | doaj.art-104dda0788d2428eac97eed7ddb9eca62023-06-12T04:27:30ZengFrontiers Media S.A.Frontiers in Immunology1664-32242023-06-011410.3389/fimmu.2023.11329391132939Inhibition of γ-glutamyl transferase suppresses airway hyperresponsiveness and airway inflammation in a mouse model of steroid resistant asthma exacerbationCancan Zhang0Huisha Xu1Keilah G. Netto2Leon A. Sokulsky3Yiyan Miao4Zhongyuan Mo5Yan Meng6Yingying Du7Chengyong Wu8Liyou Han9Lirong Zhang10Chi Liu11Guojun Zhang12Fuguang Li13Ming Yang14Ming Yang15Academy of Medical Sciences & Department of Immunology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, ChinaAcademy of Medical Sciences & Department of Immunology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, ChinaPriority Research Centre for Healthy Lungs, School of Biomedical Sciences & Pharmacy, Faculty of Health and Hunter Medical Research Institute, The University of Newcastle, Callaghan, New South Wales, AustraliaPriority Research Centre for Healthy Lungs, School of Biomedical Sciences & Pharmacy, Faculty of Health and Hunter Medical Research Institute, The University of Newcastle, Callaghan, New South Wales, AustraliaAcademy of Medical Sciences & Department of Immunology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, ChinaAcademy of Medical Sciences & Department of Immunology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, ChinaAcademy of Medical Sciences & Department of Immunology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, ChinaAcademy of Medical Sciences & Department of Immunology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, ChinaAcademy of Medical Sciences & Department of Immunology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, ChinaInstitute for Liberal Arts and Sciences, Kyoto University, Kyoto, JapanDepartment of Pharmacology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, ChinaDepartment of Physiology, School of Basic Medicine Science, Central South University, Changsha, ChinaDepartment of Pulmonary and Critical Care Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaAcademy of Medical Sciences & Department of Immunology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, ChinaAcademy of Medical Sciences & Department of Immunology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, ChinaPriority Research Centre for Healthy Lungs, School of Biomedical Sciences & Pharmacy, Faculty of Health and Hunter Medical Research Institute, The University of Newcastle, Callaghan, New South Wales, AustraliaIntroductionDespite recent advances, there are limited treatments available for acute asthma exacerbations. Here, we investigated the therapeutic potential of GGsTop, a γ-glutamyl transferase inhibitor, on the disease with a murine model of asthma exacerbation.MethodsGGsTop was administered to mice that received lipopolysaccharide (LPS) and ovalbumin (OVA) challenges. Airway hyperresponsiveness (AHR), lung histology, mucus hypersecretion, and collagen deposition were analyzed to evaluate the hallmark features of asthma exacerbation. The level of proinflammatory cytokines and glutathione were determined with/without GGsTop. The transcription profiles were also examined.ResultsGGsTop attenuates hallmark features of the disease with a murine model of LPS and OVA driven asthma exacerbation. Airway hyperresponsiveness (AHR), mucus hypersecretion, collagen deposition, and expression of inflammatory cytokines were dramatically inhibited by GGsTop treatment. Additionally, GGsTop restored the level of glutathione. Using RNA-sequencing and pathway analysis, we demonstrated that the activation of LPS/NFκB signaling pathway in airway was downregulated by GGsTop. Interestingly, further analysis revealed that GGsTop significantly inhibited not only IFNγ responses but also the expression of glucocorticoid-associated molecules, implicating that GGsTop profoundly attenuates inflammatory pathways.ConclusionsOur study suggests that GGsTop is a viable treatment for asthma exacerbation by broadly inhibiting the activation of multiple inflammatory pathways.https://www.frontiersin.org/articles/10.3389/fimmu.2023.1132939/fullasthma exacerbationLPSγ-glutamyl transferaseairway hyperresponsivenessairway inflammation |
| spellingShingle | Cancan Zhang Huisha Xu Keilah G. Netto Leon A. Sokulsky Yiyan Miao Zhongyuan Mo Yan Meng Yingying Du Chengyong Wu Liyou Han Lirong Zhang Chi Liu Guojun Zhang Fuguang Li Ming Yang Ming Yang Inhibition of γ-glutamyl transferase suppresses airway hyperresponsiveness and airway inflammation in a mouse model of steroid resistant asthma exacerbation Frontiers in Immunology asthma exacerbation LPS γ-glutamyl transferase airway hyperresponsiveness airway inflammation |
| title | Inhibition of γ-glutamyl transferase suppresses airway hyperresponsiveness and airway inflammation in a mouse model of steroid resistant asthma exacerbation |
| title_full | Inhibition of γ-glutamyl transferase suppresses airway hyperresponsiveness and airway inflammation in a mouse model of steroid resistant asthma exacerbation |
| title_fullStr | Inhibition of γ-glutamyl transferase suppresses airway hyperresponsiveness and airway inflammation in a mouse model of steroid resistant asthma exacerbation |
| title_full_unstemmed | Inhibition of γ-glutamyl transferase suppresses airway hyperresponsiveness and airway inflammation in a mouse model of steroid resistant asthma exacerbation |
| title_short | Inhibition of γ-glutamyl transferase suppresses airway hyperresponsiveness and airway inflammation in a mouse model of steroid resistant asthma exacerbation |
| title_sort | inhibition of γ glutamyl transferase suppresses airway hyperresponsiveness and airway inflammation in a mouse model of steroid resistant asthma exacerbation |
| topic | asthma exacerbation LPS γ-glutamyl transferase airway hyperresponsiveness airway inflammation |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1132939/full |
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