Rapid burst of H2O2 by plant growth regulators increases intracellular Ca2+ amounts and modulates CD4+ T cell activation.
The identification of small molecules that affect T cell activation is an important area of research. Three molecules that regulate plant growth and differentiation, but not their structurally similar analogs, were identified to enhance primary mouse CD4(+) T cell activation in conjunction with soluble anti-CD3 stimulation: Indoleacetic acid (natural plant auxin), 1-Napthaleneacetic acid (synthetic plant auxin) and 2,4-Dichlorophenoxyacetic acid (synthetic plant auxin and herbicide). These effects are distinct in comparison to Curcumin, the well known phenolic immunomodulator, which lowers T cell activation. An investigation into the mechanisms of action of the three plant growth regulators revealed a rapid induction of reactive oxygen species (ROS), mainly comprising H(2)O(2). In addition, these three molecules synergize with soluble anti-CD3 signaling to enhance intracellular Ca(2+) concentrations [Ca(2+)](i), leading to greater T cell activation, e.g. induction of CD25 and IL-2. Enhanced production of TNFα and IFNγ by CD4(+) T cells is also observed upon plant growth regulator treatment with soluble anti-CD3. Interestingly, maximal IL-2 production and CD4(+) T cell cycle progression are observed upon activation with soluble anti-CD3 and phorbol 12-myristate 13-acetate (PMA), a phorbol ester. Additionally, stimulation with PMA and Ionomcyin (a Ca(2+) ionophore), which activates T cells by circumventing the TCR, and plant growth regulators also demonstrated the role of the strength of signal (SOS): T cell cycle progression is enhanced with gentle activation conditions but decreased with strong activation conditions. This study demonstrates the direct effects of three plant growth regulators on CD4(+) T cell activation and cycling.
Ahmed
Asma
A
Department of Biochemistry, Indian Institute of Science, Bangalore, India.
Mukherjee
Sambuddho
S
Deobagkar
Mukta
M
Naik
Tanushree
T
Nandi
Dipankar
D
D015084:2,4-Dichlorophenoxyacetic Acid / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D017252:CD3 Complex / Q000276:immunology / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D002118:Calcium / Q000276:immunology / Q000378:metabolism*; D002453:Cell Cycle / Q000187:drug effects / Q000276:immunology; D003474:Curcumin / Q000494:pharmacology; D005260:Female; D006861:Hydrogen Peroxide / Q000276:immunology / Q000378:metabolism*; D007210:Indoleacetic Acids / Q000737:chemistry / Q000494:pharmacology*; D007371:Interferon-gamma / Q000276:immunology; D007376:Interleukin-2 / Q000276:immunology / Q000378:metabolism; D015759:Ionomycin / Q000276:immunology / Q000494:pharmacology; D008213:Lymphocyte Activation; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009280:Naphthaleneacetic Acids / Q000737:chemistry / Q000494:pharmacology*; D010937:Plant Growth Regulators / Q000737:chemistry / Q000494:pharmacology*; D011948:Receptors, Antigen, T-Cell / Q000276:immunology / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000276:immunology; D013755:Tetradecanoylphorbol Acetate / Q000276:immunology / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000378:metabolism
D017252:CD3 Complex; D007210:Indoleacetic Acids; D007376:Interleukin-2; D009280:Naphthaleneacetic Acids; D010937:Plant Growth Regulators; D011948:Receptors, Antigen, T-Cell; D014409:Tumor Necrosis Factor-alpha; D015084:2,4-Dichlorophenoxyacetic Acid; C034182:1-naphthaleneacetic acid; D015759:Ionomycin; C030737:indoleacetic acid; D007371:Interferon-gamma; D006861:Hydrogen Peroxide; D003474:Curcumin; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium