Immunomodulatory effects in the spleen-injured mice following exposure to titanium dioxide nanoparticles

J Biomed Mater Res A. 2014 Oct;102(10):3562-72. doi: 10.1002/jbm.a.35034. Epub 2013 Nov 16.


Immune injuries following the exposure of titanium dioxide nanoparticles (TiO₂ NPs) have been greatly concerned along with the TiO₂ NPs are widely used in pharmacology and daily life. However, very little is known about the immunomodulatory mechanisms in the spleen-injured mice due to TiO₂ NPs exposure. In this study, mice were continuously exposed to 2.5, 5, or 10 TiO₂ NPs mg kg(-1) body weight for 90 days with intragastric administration to investigate the immunomodulatory mechanisms in the spleen. The findings showed that TiO₂ NPs exposure resulted in significant increases in spleen and thymus indices, and titanium accumulation, in turn led to histopathological changes and splenocyte apoptosis. Furthermore, the exposure of TiO₂ NPs could significantly increase the levels of macrophage inflammatory protein (MIP)-1α, MIP-2, Eotaxin, monocyte chemotactic protein-1, interferon-γ, vascular cell adhesion molecule-1, interleukin-13, interferon-γ-inducible protein-10, migration inhibitory factor, CD69, major histocompatibility complex, protein tyrosine phosphatase, protein tyrosine kinase 1, basic fibroblast growth factor, Fasl, and GzmB expression, whereas markedly decrease the levels of NKG2D, NKp46, 2B4 expression involved in immune responses, lymphocyte healing and apoptosis. These findings would better understand toxicological effects induced by TiO₂ NPs exposure.

Keywords: immunomodulation; immunotoxicity; mice; spleen injury; titanium dioxide nanoparticles.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Body Weight / drug effects
  • Chemokines / metabolism
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Gene Expression Regulation / drug effects
  • Immunologic Factors / pharmacology*
  • Inflammation Mediators / metabolism
  • Mice
  • Nanoparticles / chemistry*
  • Organ Specificity / drug effects
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Real-Time Polymerase Chain Reaction
  • Spleen / drug effects
  • Spleen / immunology*
  • Spleen / injuries*
  • Spleen / pathology
  • Titanium / administration & dosage
  • Titanium / pharmacology*


  • Chemokines
  • Immunologic Factors
  • Inflammation Mediators
  • RNA, Messenger
  • titanium dioxide
  • Titanium