title: A role of cellular glutathione in the differential effects of iron oxide nanoparticles on antigen-specific T cell cytokine expression.
abstract: BACKGROUND
  Accumulating evidence indicates that iron oxide nanoparticles modulate immune responses, and induce oxidative stress in macrophages. It was recently reported that iron oxide nanoparticles attenuated antigen-specific immunity in vivo, though the underlying mechanism remains elusive. The present study investigates the direct effect of iron oxide nanoparticles on antigen-specific cytokine expression by T cells, and potential underlying mechanisms.
  
  
  METHODS
  Ovalbumin-primed splenocytes were exposed to iron oxide nanoparticles, followed by restimulation with ovalbumin. Cell viability, cytokine production, and cellular levels of glutathione and reactive oxygen species were measured.
  
  
  RESULTS
  The splenocyte viability and the production of interleukin-2 and interleukin-4 were unaffected, whereas interferon-γ production was markedly attenuated by iron oxide nanoparticles (10-100 μg iron/mL) in a concentration-dependent manner. Iron oxide nanoparticles also transiently diminished the intracellular level of glutathione, with a peak response at 6 hours posttreatment. The effects of iron oxide nanoparticles on interferon-γ and glutathione were attenuated by the presence of N-acetyl-L-cysteine, a precursor of glutathione. However, iron oxide nanoparticles did not influence the generation of reactive oxygen species.
  
  
  CONCLUSIONS
  Iron oxide nanoparticles induced a differential effect on antigen-specific cytokine expression by T cells, in which the T helper 1 cytokine IFN-γ was sensitive, whereas the T helper 2 cytokine interleukin-4 was refractory. In addition, the suppressive effect of iron oxide nanoparticles on interferon-γ was closely associated with the diminishment of glutathione.
authors: Department and Graduate Institute of Veterinary Medicine, School of Veterinary Medicine, National Taiwan University, Taipei, Taiwan.
authors: Chien-Chang
authors: CC
authors: Shen
authors: Hong-Jen
authors: HJ
authors: Liang
authors: Chia-Chi
authors: CC
authors: Wang
authors: Mei-Hsiu
authors: MH
authors: Liao
authors: Tong-Rong
authors: TR
authors: Jan
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D016207:Cytokines / Q000096:biosynthesis*; D005290:Ferric Compounds / Q000737:chemistry / Q000494:pharmacology*; D005978:Glutathione / Q000378:metabolism*; D007371:Interferon-gamma / Q000096:biosynthesis; D007378:Interleukins / Q000096:biosynthesis; D058185:Magnetite Nanoparticles / Q000737:chemistry*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin; D017382:Reactive Oxygen Species / Q000378:metabolism; D013154:Spleen / Q000166:cytology; D013601:T-Lymphocytes / Q000187:drug effects* / Q000378:metabolism
chemical_list: D000975:Antioxidants; D016207:Cytokines; D005290:Ferric Compounds; D007378:Interleukins; D058185:Magnetite Nanoparticles; D017382:Reactive Oxygen Species; C000499:ferric oxide; D007371:Interferon-gamma; D010047:Ovalbumin; D005978:Glutathione