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The AKT inhibitor MK2206 suppresses airway inflammation and the pro‑remodeling pathway in a TDI‑induced asthma mouse model

  • Authors:
    • Haiyan Cui
    • Yuanxiong Cheng
    • Yi He
    • Weiying Cheng
    • Wenqu Zhao
    • Haijin Zhao
    • Fiona H. Zhou
    • Liping Wang
    • Jianghui Dong
    • Shaoxi Cai
  • View Affiliations / Copyright

    Affiliations: Department of Respiratory and Critical Care Medicine, Chronic Airway Disease Laboratory, Nanfang Hospital of Southern Medical University, Guangzhou, Guangdong 510000, P.R. China, Department of Respiratory and Critical Care Medicine, The Third Affiliated Hospital of Southern Medical University, Guangzhou, Guangdong 510630, P.R. China, Department of Immunology Medicine, The Third Affiliated Hospital of Southern Medical University, Guangzhou, Guangdong 510630, P.R. China, UniSA Clinical and Health Sciences, UniSA Cancer Research Institute, University of South Australia, Adelaide, South Australia 5001, Australia
    Copyright: © Cui et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 3723-3734
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    Published online on: August 21, 2020
       https://doi.org/10.3892/mmr.2020.11450
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Abstract

The cellular and molecular mechanisms via which MK2206, an AKT inhibitor, prevents the activation of AKT in toluene diisocyanate (TDI)‑induced asthma remain unclear. Thus, the present study aimed to evaluate the potential effects of MK2206 on airway AKT activation, inflammation and remodeling in a TDI‑induced mouse model of asthma. A total of 24 BALB/c mice were selected and randomly divided into untreated (AOO), asthma (TDI), MK2206 (TDI + MK2206), and dexamethasone (TDI + DEX) groups. Phosphorylated AKT (p‑AKT), total AKT, airway remodeling indices, α‑smooth muscle actin (α‑SMA) and collagen I levels in pulmonary tissue were measured using western blotting. Airway inflammation factors, including interleukin (IL)‑4, ‑5, ‑6, and ‑13 in bronchoalveolar lavage fluid (BALF) and IgE in serum, were determined using ELISA. Additionally, the airway hyperresponsiveness (AHR) and pulmonary pathology of all groups were evaluated. The results of the present study demonstrated that p‑AKT levels in lung protein lysate were upregulated, and neutrophil, eosinophil and lymphocyte counts were increased in the lungs obtained from the asthma group compared with the AOO group. Both MK2206 and DEX treatment in TDI‑induced mice resulted not only in the attenuation of AKT phosphorylation, but also reductions in neutrophil, eosinophil and lymphocyte counts in the lungs of mice in the asthma group. Consistently, increases in the levels of the inflammatory cytokines IL‑4, ‑5, ‑6 and ‑13 analyzed in BALF, and serum IgE in the TDI group were demonstrated to be attenuated in the TDI + MK2206 and TDI + DEX groups. Furthermore, α‑SMA and AHR were significantly attenuated in the TDI + MK2206 group compared with the TDI group. These results revealed that MK2206 not only inhibited AKT activation, but also served a role in downregulating airway inflammation and airway remodeling in chemical‑induced asthma. Therefore, the findings of the present study may provide important insight into further combination therapy.
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Copy and paste a formatted citation
Spandidos Publications style
Cui H, Cheng Y, He Y, Cheng W, Zhao W, Zhao H, Zhou FH, Wang L, Dong J, Cai S, Cai S, et al: The AKT inhibitor MK2206 suppresses airway inflammation and the pro‑remodeling pathway in a TDI‑induced asthma mouse model. Mol Med Rep 22: 3723-3734, 2020.
APA
Cui, H., Cheng, Y., He, Y., Cheng, W., Zhao, W., Zhao, H. ... Cai, S. (2020). The AKT inhibitor MK2206 suppresses airway inflammation and the pro‑remodeling pathway in a TDI‑induced asthma mouse model. Molecular Medicine Reports, 22, 3723-3734. https://doi.org/10.3892/mmr.2020.11450
MLA
Cui, H., Cheng, Y., He, Y., Cheng, W., Zhao, W., Zhao, H., Zhou, F. H., Wang, L., Dong, J., Cai, S."The AKT inhibitor MK2206 suppresses airway inflammation and the pro‑remodeling pathway in a TDI‑induced asthma mouse model". Molecular Medicine Reports 22.5 (2020): 3723-3734.
Chicago
Cui, H., Cheng, Y., He, Y., Cheng, W., Zhao, W., Zhao, H., Zhou, F. H., Wang, L., Dong, J., Cai, S."The AKT inhibitor MK2206 suppresses airway inflammation and the pro‑remodeling pathway in a TDI‑induced asthma mouse model". Molecular Medicine Reports 22, no. 5 (2020): 3723-3734. https://doi.org/10.3892/mmr.2020.11450
Copy and paste a formatted citation
x
Spandidos Publications style
Cui H, Cheng Y, He Y, Cheng W, Zhao W, Zhao H, Zhou FH, Wang L, Dong J, Cai S, Cai S, et al: The AKT inhibitor MK2206 suppresses airway inflammation and the pro‑remodeling pathway in a TDI‑induced asthma mouse model. Mol Med Rep 22: 3723-3734, 2020.
APA
Cui, H., Cheng, Y., He, Y., Cheng, W., Zhao, W., Zhao, H. ... Cai, S. (2020). The AKT inhibitor MK2206 suppresses airway inflammation and the pro‑remodeling pathway in a TDI‑induced asthma mouse model. Molecular Medicine Reports, 22, 3723-3734. https://doi.org/10.3892/mmr.2020.11450
MLA
Cui, H., Cheng, Y., He, Y., Cheng, W., Zhao, W., Zhao, H., Zhou, F. H., Wang, L., Dong, J., Cai, S."The AKT inhibitor MK2206 suppresses airway inflammation and the pro‑remodeling pathway in a TDI‑induced asthma mouse model". Molecular Medicine Reports 22.5 (2020): 3723-3734.
Chicago
Cui, H., Cheng, Y., He, Y., Cheng, W., Zhao, W., Zhao, H., Zhou, F. H., Wang, L., Dong, J., Cai, S."The AKT inhibitor MK2206 suppresses airway inflammation and the pro‑remodeling pathway in a TDI‑induced asthma mouse model". Molecular Medicine Reports 22, no. 5 (2020): 3723-3734. https://doi.org/10.3892/mmr.2020.11450
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