Trichomonas vaginalis inhibits proinflammatory cytokine production in macrophages by suppressing NF-kappaB activation

Mol Cells. 2004 Oct 31;18(2):177-85.


Activation of NF-kappaB leads to the production of proinflammatory cytokines such as IL-12 and TNF-alpha that are involved in innate and adaptive immunity. We determined whether T. vaginalis-induced inflammatory response in macrophages associated with NF-kappaB. T. vaginalis adhesion led to transient NF-kappaB activation at 6 h but activation declined dramatically by 8 h. Super-shift assays showed that the gel-shifted complexes consisted of p65 (Rel A) and p50 (NF-kappaB1). NF-kappaB activation was accompanied by IkappaB-alpha degradation, and was inhibited by blocking T. vaginalis adhesion, indicating that the early NF-kappaB activation by T. vaginalis depends on IkappaB-alpha degradation. Quantitative real-time RT-PCR analyses revealed that the expression of TNF-alpha and IL-12 mRNA in T. vaginalis-adhesive cells was rapidly suppressed in comparison with LPS stimulation. We also observed that the parasite inhibited the nuclear translocation of NF-kappaB at 8 h, and diminished IL-12 and TNF-alpha production in response to LPS. In addition, inhibition of IkappaB-alpha degradation by MG-132 resulted in apoptosis. These results demonstrate that effects of T. vaginalis on NF-kappaB regulation are critical for cytokine production and the survival of macrophages. We suggest that there exist inhibitory mechanisms induced by T. vaginalis to evade host immunity.

MeSH terms

  • Animals
  • Cell Survival
  • Cytokines / antagonists & inhibitors*
  • Cytokines / biosynthesis
  • Enzyme Activation
  • I-kappa B Proteins / metabolism
  • Immunity
  • Inflammation / parasitology
  • Interleukin-12 / genetics
  • Kinetics
  • Macrophages / parasitology*
  • Mice
  • NF-KappaB Inhibitor alpha
  • NF-kappa B / antagonists & inhibitors*
  • NF-kappa B / metabolism
  • NF-kappa B p50 Subunit
  • RNA, Messenger / analysis
  • Transcription Factor RelA
  • Transcription Factors / antagonists & inhibitors
  • Trichomonas Infections / immunology
  • Trichomonas vaginalis / immunology*
  • Tumor Necrosis Factor-alpha / genetics


  • Cytokines
  • I-kappa B Proteins
  • NF-kappa B
  • NF-kappa B p50 Subunit
  • Nfkbia protein, mouse
  • RNA, Messenger
  • Transcription Factor RelA
  • Transcription Factors
  • Tumor Necrosis Factor-alpha
  • NF-KappaB Inhibitor alpha
  • Nfkb1 protein, mouse
  • Interleukin-12