Propofol attenuates mast cell degranulation via inhibiting the miR-221/PI3K/Akt/Ca2+ pathway

Zhiyong Yi; Zhipan Yi; Kai Huang; Yanqun Cao; Chuli Xiao; Yanwei Li; Quzhe Lu; Shuang Zhao; Wenqi Luo; Guanlan Liu

doi:10.3892/etm.2018.6317

Propofol attenuates mast cell degranulation via inhibiting the miR-221/PI3K/Akt/Ca²⁺ pathway

Exp Ther Med. 2018 Aug;16(2):1426-1432. doi: 10.3892/etm.2018.6317. Epub 2018 Jun 15.

Authors

Zhiyong Yi¹, Zhipan Yi², Kai Huang¹, Yanqun Cao¹, Chuli Xiao¹, Yanwei Li¹, Quzhe Lu¹, Shuang Zhao¹, Wenqi Luo^{3

4}, Guanlan Liu³

Affiliations

¹ Department of Human Anatomy and Histology-Embryology, Medical School, Shaoyang University, Shaoyang, Hunan 422000, P.R. China.
² Pharmaceutical Preparation Section, Shaoyang Maternity and Child Health Care Hospital, Shaoyang, Hunan 422001, P.R. China.
³ Department of Histology and Embryology, Changsha Medical University, Changsha, Hunan 410219, P.R. China.
⁴ Department of Respiratory Medicine, The First Affiliated Hospital, Changsha Medical University, Changsha, Hunan 410219, P.R. China.

Abstract

The aim of the present study was to investigate the effect of propofol on immunoglobulin (Ig)E-activated mast cell degranulation and explore the underlying mechanisms responsible. RBL-2H3 cells were treated with propofol for at a variety of concentrations and different amounts of time. Cell viability was assessed using an MTT assay and microRNA (miR)-221 expression was quantified using reverse transcription-quantitative polymerase chain reaction. RBL-2H3 cells were transfected with miR-221 mimic or a negative control and degranulation, including the release of β-hexosaminidase and histamine, was evaluated using an ELISA kit. The effect of miR-221 overexpression on the phosphorylation of protein kinase B (Akt) was detected using western blotting and extracellular Ca²⁺ influx was measured via afura-2 assay. The phosphoinositide 3-kinase(PI3K) inhibitor LY294002 was used to investigate the association between PI3K/Akt signaling and Ca²⁺ influx in the presence of propofol. The results demonstrated that propofol treatment suppressed RBL-2H3 cell proliferation in a dose- and time-dependent manner. Propofol inhibited miR-221 expression in a dose-dependent manner compared with the control group; however, the inhibitive effect was significantly abrogated following transfection with miR-221 mimics. Furthermore, β-hexosaminidase and histamine release, PI3K/Akt signaling and Ca²⁺ influx were decreased following propofol application. miR-221 overexpression markedly ameliorated the suppressive effect of propofol. Treatment with LY294002 reversed the propofol-induced decrement of Ca²⁺ influx on IgE-mediated RBL-2H3 cells, suggesting an association between PI3K/Akt signaling and Ca²⁺ influx. In conclusion, the results of the present study suggest that propofol treatment attenuates mast cell degranulation via inhibiting the miR-221/PI3K/Akt/Ca²⁺ pathway. These results indicate that propofol may have a potential therapeutic effect as a treatment for allergic diseases.

Keywords: Ca2+ influx; RBL-2H3 cells; mast cell degranulation; microRNA-221; phosphoinositide 3-kinase/protein kinase B pathway; propofol.