Activation of NF-κB leads to the production of proinflammatory cytokines such as IL-12 and TNF-α that are involved in innate and adaptive immunity. We determined whether T. vaginalis-induced inflammatory response in macrophages associated with NF-κB. T. vaginalis adhesion led to transient NF-κB 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-κB1). NF-κB activation was accompanied by IκB-α degradation, and was inhibited by blocking T. vaginalis adhesion, indicating that the early NF-κB activation by T. vaginalis depends on IkB-α degradation. Quantitative real-time RT-PCR analyses revealed that the expression of TNF-α 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-κB at 8 h, and diminished IL-12 and TNF-α production in response to LPS. In addition, inhibition of Iκ B-α degradation by MG-132 resulted in apoptosis. These results demonstrate that effects of T. vaginalis on NF-κB 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.
|Number of pages||9|
|Journal||Molecules and cells|
|Publication status||Published - 2004 Oct 31|
All Science Journal Classification (ASJC) codes
- Molecular Biology
- Cell Biology