In vitro stimulatory effect of N-acetyl tryptophan-glucopyranoside against gamma radiation induced immunosuppression

Environ Toxicol. 2018 Mar;33(3):305-314. doi: 10.1002/tox.22517. Epub 2017 Dec 4.

Abstract

Radiation-induced manifestations like free radical burst, oxidative damage and apoptosis leading to cell death. In present study, N-acetyl tryptophan glucopyranoside (NATG) was assessed for its immune-radioprotective activities using J774A.1 cells. Clonogenic cell survival, cell cycle progression and cytokines i.e. IFN-γ, TNF-α, IL-2, IL-10, IL-12, IL-13 and IL-17A expression were evaluated in irradiated and NATG pretreated cells using clonogenic formation ability, flow cytometry and ELISA assay. Results indicated that 0.25μg/ml NATG exhibited maximum radioprotection against gamma-radiation (2Gy) without intervening in cell cycle progression. NATG pretreated (-2 h) plus irradiated cells showed significant elevation in IFN-γ (∼38.2%), IL-17A (∼53.7%) and IL-12 (∼58.8%) expression as compared to only irradiated cells. Conversely, significant decrease in TNF-α (∼21.6%), IL-10 (∼31.2%), IL-2 (∼23.7%) and IL-13 expression (∼17.8%) were observed in NATG pretreated plus irradiated cells as compared to irradiated cells. Conclusively, NATG pretreatment to irradiated J774A.1 cells, stimulate Th1 while diminish Th2 cytokines that contributes to radioprotection.

Keywords: Th1/Th2 homeostasis; cell cycle progression; cytokines; immune response; ionizing radiation; radioprotection.

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Apoptosis / radiation effects
  • Cell Cycle / drug effects
  • Cell Cycle / radiation effects
  • Cell Line
  • Gamma Rays / adverse effects
  • Immunologic Factors / pharmacology*
  • Immunosuppression Therapy*
  • Interferon-gamma / metabolism
  • Interleukin-10
  • Interleukin-13 / metabolism
  • Interleukin-17 / metabolism
  • Interleukin-2 / metabolism
  • Macrophages / immunology
  • Macrophages / metabolism
  • Macrophages / radiation effects
  • Mice
  • Radiation-Protective Agents / pharmacology*
  • Th1-Th2 Balance
  • Tryptophan / analogs & derivatives
  • Tryptophan / pharmacology
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • IL10 protein, human
  • IL17A protein, human
  • Immunologic Factors
  • Interleukin-13
  • Interleukin-17
  • Interleukin-2
  • N-acetyl tryptophan-glucopyranoside
  • Radiation-Protective Agents
  • Tumor Necrosis Factor-alpha
  • Interleukin-10
  • Interferon-gamma
  • Tryptophan