Manganese promotes phorbol ester-induced interleukin-2 production via AP-1 activation in Jurkat T-cells

Area of Science:

• Immunology
• Cellular Biology
• Nutritional Biochemistry

Background:

• Manganese (Mn²⁺) is an essential trace element vital for numerous enzymatic activities and cellular functions.
• The precise physiological roles and potential toxicity of Mn²⁺, particularly within the immune system, require further elucidation.
• Interleukin-2 (IL-2) is a critical cytokine for T-cell proliferation and immune response modulation.

Purpose of the Study:

• To investigate the pharmacological effects and toxicity of Mn²⁺ on the immune system.
• To specifically examine the influence of Mn²⁺ on interleukin-2 (IL-2) production in Jurkat T-cells.

Main Methods:

• Jurkat T-cells were treated with varying concentrations of Mn²⁺ and phorbol 12-myristate 13-acetate (PMA).
• IL-2 production was quantified, and reporter gene assays were employed to assess activator protein-1 (AP-1) activity.
• Western blot analysis was utilized to examine the activation of c-Jun N-terminal kinase 2 (JNK2) and p38 mitogen-activated protein kinase (MAPK), as well as c-Fos and c-Jun expression.

Main Results:

• Mn²⁺ alone did not significantly induce IL-2 production, but it dose-dependently enhanced PMA-induced IL-2 production at concentrations of 0.3-0.7 mM.
• Mn²⁺ promoted AP-1 activity in the presence of PMA, as indicated by reporter gene assays.
• Western blot analysis revealed that Mn²⁺ enhanced the activation of JNK2 and p38 MAPK, leading to increased c-Fos and c-Jun production within 4 hours.

Conclusions:

• Mn²⁺ plays a significant role in modulating T-cell responses by enhancing IL-2 production.
• The mechanism involves the induction of AP-1 activity through the activation of JNK2 and p38 MAPK pathways, leading to increased c-Fos and c-Jun.
• These findings highlight the immunomodulatory potential of Mn²⁺ and suggest its involvement in regulating cellular immune functions.