P38 MAPK/AKT signalling is involved in IL-33-mediated anti-apoptosis in childhood acute lymphoblastic leukaemia blast cells

Annals of Medicine

Zeyu Zhu¹  Jie Yang²  Xindan Lian²  Hanyi Hou³  Haibo Su⁴  Yiqian Wang⁴  Qing Gong⁴  Xuexin Chen⁴  Zhongping Liang⁴  Huanmin Luo⁵ 

[1]KingMed School of Laboratory Medicine, Guangzhou Medical University, Guangzhou, China

[2]School of Pediatrics, Guangzhou Medical University, Guangzhou, China

[3]The Second Clinical Medicine School, Guangzhou Medical University, Guangzhou, China

[4]The Sixed Affiliated Hospital, GMU-GIBH Joint School of Life Sciences, Guangzhou Medical University, Guangzhou, China

[5]The Third Clinical Medicine School, Guangzhou Medical University, Guangzhou, China

关键词: ALL;    IL1RL1;    IL-33;    P38 MAPK;    AKT;    anti-apoptosis;   

DOI  :  10.1080/07853890.2021.1970217

来源: DOAJ

【 摘 要 】

Background Acute lymphoblastic leukaemia (ALL) is often characterized by broad clinical and biological heterogeneity, as well as recurrent genetic aberrations. Despite remarkable improvements in the treatment outcome in paediatric ALL over the past several decades, it remains a leading cause of morbidity and mortality among children. Cytokines have been extensively studied in haematologic diseases; however, the mechanisms by which cytokines contribute to ALL pathogenesis remain poorly understood.Methods IL-33 levels were measured by enzyme-linked immunosorbent assay (ELISA). IL1RL1 expression on ALL cell surface was accessed by flow cytometry. Expression of phosphorylated p38 MAPK, p38, pAKT, AKT and GAPDH were quantified by western blot. Cell survival signals were evaluated by apoptosis using flow cytometry.Results BM samples from ALL patients at diagnosis upregulated their cell surface expression of IL1RL1, and a higher interleukin (IL)-33 level in the serum was observed as compared to the healthy individuals. Moreover, exogenous IL-33 treatment significantly inhibited apoptosis by activating p38 mitogen-activated protein kinase (MAPK) and AKT pathway, while the inhibitor for p38 MAPK, SB203580, counteracted IL-33-induced anti-apoptosis via inactivation of p38 MAPK and AKT. Furthermore, IL-33 negatively regulates cyclin B1 protein level while increasing the expression of CDK1, with SB203580 inhibiting the effect.Conclusion Our study reveals an important role for IL-33/IL1RL1 axis in supporting ALL which may represent a novel treatment for paediatric patients.KEY MESSAGESBoth IL-33 and IL1RL1 levels are upregulated in primary ALL samples.IL-33 increased both p38 MAPK and AKT activation in ALL.IL-33 promotes survival and cell cycle progression of ALL cells via activating p38 MAPK.

【 授权许可】

Unknown