Effect of selenite on T-cell mitogenesis: contribution of ROS production and apoptosis signal-regulating kinase 1

Area of Science:

• Immunology
• Cell Biology
• Biochemistry

Background:

• Sodium selenite enhances T-cell mitogenesis, but underlying mechanisms are unclear.
• Investigating selenite's impact on T-cell responses requires understanding its effects on apoptosis, tumor necrosis factor-alpha (TNF-alpha), reactive oxygen species (ROS), apoptosis signal-regulating kinase 1 (ASK1), and the thioredoxin (Trx) system.

Purpose of the Study:

• To elucidate the mechanisms by which sodium selenite stimulates T-cell mitogenesis.
• To evaluate the interplay between selenite, ROS, apoptosis, ASK1, and the Trx system in T-cells.

Main Methods:

• Mouse splenocytes were treated with varying concentrations of sodium selenite.
• Measurements included TNF-alpha release, apoptosis induction, ROS accumulation, and expression of phospho-ASK1, Trx reductase 1, and Trx-1.
• Experiments utilized wild-type and Trx-1-transgenic mouse splenocytes.

Main Results:

• Selenite induced dose-dependent TNF-alpha release and apoptosis.
• Low selenite concentrations inhibited ROS accumulation and induced apoptosis in wild-type splenocytes, alongside increased Trx reductase 1 expression.
• Apoptosis suppression correlated with decreased phospho-ASK1 expression, particularly in Trx-1-transgenic splenocytes at high selenite concentrations.

Conclusions:

• Selenite-induced T-cell mitogenesis is partly mediated by ROS inhibition.
• This involves the Trx system, ASK1 inactivation, and subsequent apoptosis suppression.
• Findings clarify selenite's immunomodulatory effects at the molecular level.