Honokiol induces apoptosis and autophagy in dexamethasone-resistant T-acute lymphoblastic leukemia CEM-C1 cells.

Objective: To study whether and, if so, how honokiol overcome dexamethasone resistance in DEX-resistant CEM-C1 cells. Methods: We investigated the effect of honokiol (0-20 µM) on cell proliferation, cell cycle, cell apoptosis and autophagy in DEX-resistant CEM-C1 cells and DEX-sensitive CEM-C7 cells. We also determined the role of c-Myc protein and mRNA in the occurrence of T-ALL associated dexamethasone resistance western blot and reverse transcription-qPCR (RT-qPCR) analysis. Results: Cell Counting Kit (CCK)-8 assay shows that DEX-resistant CEM-C1 cell lines were highly resistant to dexamethasone with IC50 of 364.1 ± 29.5 µM for 48 h treatment. However, upon treatment with dexamethasone in combination with 1.5 µM of honokiol for 48 h, the IC50 of CEM-C1 cells significantly decreased to 126.2 ± 12.3 µM, and the reversal fold was 2.88. Conversely, the IC50 of CEM-C7 cells was not changed combination of dexamethasone and honokiol as compared to that of CEM-C7 cells treated with dexamethasone alone. It has been shown that honokiol induced T-ALL cell growth inhibition by apoptosis and autophagy via downregulating cell cycle-regulated proteins (Cyclin E, CDK4, and Cyclin D1) and anti-apoptotic proteins BCL-2 and upregulating pro-apoptotic proteins Bax and led to PARP cleavage. Honokiol may overcome dexamethasone resistance in DEX-resistant CEM-C1 cell lines via the suppression of c-Myc mRNA expression. Conclusion: The combination of honokiol and DEX were better than DEX alone in DEX-resistant CEM-C1 cell lines. Honokiol may regulate T-ALL-related dexamethasone resistance by affecting c-Myc.

IL-21 alleviates allergic asthma in DOCK8-knockout mice.

Patients with DOCK8 deficiency are at increased susceptibility to develop allergic diseases such as food allergy and asthma. Here, we aimed to analyze the pathogenesis of asthma in DOCK8-deficient patients. In our mouse model, DOCK8-knockout (KO) mice sensitized with low-dose OVA were challenged with 1.5% OVA to induce allergic asthma. As compared to that in WT mice, remarkable airway hyperresponsiveness was observed in KO mice. Increased inflammatory cells and eosinophils infiltrated in airway lumen in KO mice especially around bronchi. KO mice showed higher levels of serum IgE and OVA-specific IgE and significantly elevated IgE-producing B cells in blood and in spleen. Surprisingly, nasal administration with rmIL-21 significantly reduced the airway hyperresponsiveness, inflammatory infiltration, as well as the serum IgE and IgE-producing B cells. DOCK8-knockout mice are susceptible to low-dose OVA induced allergic airway inflammation and airway hyperresponsiveness. Supplementary nasal administration of rmIL-21 alleviates allergic asthma in this mouse model.