In vitro arsenic trioxide induces apoptosis in T cells of asthmatic patients by a Bcl-2 related mechanism.
- Author:
Dong-Yun QIN
1
;
Ren HUANG
;
Tie WU
Author Information
1. Department of Pharmacology, Guangdong Medical College, Zhanjiang 524023, China.
- Publication Type:Journal Article
- MeSH:
Adult;
Anti-Asthmatic Agents;
pharmacology;
Apoptosis;
drug effects;
Arsenicals;
pharmacology;
Asthma;
metabolism;
pathology;
Enzyme-Linked Immunosorbent Assay;
Flow Cytometry;
Gene Expression Regulation;
Humans;
Interleukin-4;
metabolism;
Microscopy, Fluorescence;
Middle Aged;
Oxides;
pharmacology;
Proto-Oncogene Proteins c-bcl-2;
metabolism;
T-Lymphocytes;
metabolism;
pathology
- From:
Acta Pharmaceutica Sinica
2008;43(1):35-43
- CountryChina
- Language:English
-
Abstract:
This study examined the effects of arsenic trioxide on apoptosis and interleukin-4 release in T cells of asthmatic patients in vitro and investigated the role of Bcl-2 in the active mechanism. T cells were isolated from asthmatic patients (n = 21) and healthy controls (n = 20), and then treated with arsenic trioxide and dexamethasone. Cell apoptosis was measured using fluorescence microscopy, flow cytometry and a cytochrome c ELISA kit. Interleukin-4 levels in the serum and in supernatants from T cells were quantified by ELISA. Flow cytometric analysis and immunofluorescence studies were performed to determine Bcl-2 expression. T cells of the asthmatic patients (i. e. without treatment) exhibited decelerated spontaneous apoptosis after 24 h incubation in vitro when compared to T cells of the healthy controls. With dexamethasone treatment, an increase in apoptosis of T cells was not significantly different between both groups, irrespective of the method used. Arsenic trioxide treatment, however, significantly increased the apoptosis of T cells of the asthmatic group and showed a slight effect on the control group. In asthmatic patients, elevated levels of interleukin-4 and up-regulated Bcl-2 expression were detected. Moreover, in vitro, T cells of asthmatic patients spontaneously released more interleukin-4 and exhibited more Bcl-2 expression than T cells from the control group. Arsenic trioxide treatment significantly decreased interleukin-4 release and down-regulated Bcl-2 expression in asthmatic patients, while it only slightly affected healthy controls. Dexamethasone treatment decreased interleukin-4 release in both groups examined. It did not significantly influence Bcl-2 expression. These results suggest that arsenic trioxide induces T cell apoptosis and decreases interleukin-4 release in T cells of asthmatic patients in vitro and that down-regulation of Bcl-2 expression may be an important mechanism.
