1,25-Dihydroxyvitamin D3 regulates T lymphocyte proliferation through activation of P53 and inhibition of ERK1/2 signaling pathway in children with Kawasaki disease
X.-L. Qi, L.-L. Chen, X.-G. Sun, X.-M. Li, L.-H. Zhao, D.-J. Kong Department of Pediatrics, Linyi Central Hospital, Linyi, Shandong, China. chbell@163.com
OBJECTIVE: To study the effect of 1,25(OH)2D3 on T lymphocytes in Kawasaki disease and to further investigate its molecular mechanism.
PATIENTS AND METHODS: A total of 30 child patients was diagnosed as Kawasaki disease, 60 child patients were diagnosed as infectious fever, and 60 normal children, were selected. 4 mL peripheral blood was collected before treatment. Peripheral blood mononuclear cells were isolated and separated using the Facollin method and cultured. Flow cytometry was used to identify T cells. The cell sections were prepared for immunohistochemical staining. After T cells in each group were treated with 1,25(OH)2D3, the proteins were extracted for Western blotting.
RESULTS: Peripheral blood T cells were successfully isolated and cultured, and the maximal atoxic concentration of 1,25(OH)2D3 on T cells was 10-3 μmol/L. In T cells of child patients with Kawasaki disease, signal transducer and activator of transcription 3 (STAT3) were continuously activated, P53 apoptosis genes were inactivated, and nuclear factor κB (NF-κB) P65 pathway and extracellular signal-regulated kinase (ERK) pathway were activated. After the intervention with 1,25(OH)2D3 in vitro, STAT3 and NF-κB P65 had no significant changes, the activation of ERK1/2 signaling pathway was inhibited and the P53 protein was activated.
CONCLUSIONS: Apoptotic T cells in peripheral blood in KD cannot initiate the normal apoptosis program, so they continue to proliferate and differentiate, eventually leading to the increase and abnormal activation of T cells and the immune imbalance in the body. 1,25(OH)2D3 can inhibit the excess hyperplasia of T cells through adjusting partial signal transduction pathway.
Free PDF DownloadThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License
To cite this article
X.-L. Qi, L.-L. Chen, X.-G. Sun, X.-M. Li, L.-H. Zhao, D.-J. Kong
1,25-Dihydroxyvitamin D3 regulates T lymphocyte proliferation through activation of P53 and inhibition of ERK1/2 signaling pathway in children with Kawasaki disease
Eur Rev Med Pharmacol Sci
Year: 2017
Vol. 21 - N. 16
Pages: 3714-3722
DOI: 10.26355/eurrev_201708_13289