Activation of NF-kB leads to the production of proinflammatory cytokines such as IL-12 and TNF-a that are involved in innate and adaptive immunity. We determined whether T. vaginalis-induced inflammatory response in macrophages associated with NF-kB. T. vaginalis adhesion led to transient NF-kB activation at 6 h but activation declined dramatically by 8 h. Supershift assays showed that the gel-shifted complexes consisted of p65 (Rel A) and p50 (NF-kB1). NF-kB activation was accompanied by IkB-a degradation, and was inhibited by blocking T. vaginalis adhesion, indicating that the early NF-kB activation by T. vaginalis depends on IkB-a degradation. Quantitative real-time RT-PCR analyses revealed that the expression of TNF-a 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-kB at 8 h, and diminished IL-12 and TNF-a production in response to LPS. In addition, inhibition of IkB-a degradation by MG-132 resulted in apoptosis. These results demonstrate that effects of T. vaginalis on NF-kB 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.

Keywords: Apoptosis, Macrophage, NF-kB, Trichomonas vaginalis