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

The AKT inhibitor MK2206 suppresses airway inflammation and the pro‑remodeling pathway in a TDI‑induced asthma mouse model. Mol Med Rep. 2020 Nov;22(5):3723-3734 Authors: Cui H, Cheng Y, He Y, Cheng W, Zhao W, Zhao H, Zhou FH, Wang L, Dong J, Cai S 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 t...
Source: Molecular Medicine Reports - Category: Molecular Biology Tags: Mol Med Rep Source Type: research