title: Trichomonas vaginalis inhibits proinflammatory cytokine production in macrophages by suppressing NF-kappaB activation.
abstract: 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.
authors.affiliation: Department of Biotechnology, College of Engineering and Bioproducts Research Center, Yonsei University, Seoul 120-749, Korea.
authors.forename: Jae-Ho
authors.initials: JH
authors.lastname: Chang
authors.forename: Yong-Suk
authors.initials: YS
authors.lastname: Ryang
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Morio
authors.forename: Sang-Kyou
authors.initials: SK
authors.lastname: Lee
authors.forename: Eun-Ju
authors.initials: EJ
authors.lastname: Chang
mesh_terms: D000818:Animals; D002470:Cell Survival; D016207:Cytokines / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D004789:Enzyme Activation; D020672:I-kappa B Proteins / Q000378:metabolism; D007109:Immunity; D007249:Inflammation / Q000469:parasitology; D018664:Interleukin-12 / Q000235:genetics; D007700:Kinetics; D008264:Macrophages / Q000469:parasitology*; D051379:Mice; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000378:metabolism; D052002:NF-kappa B p50 Subunit; D012333:RNA, Messenger / Q000032:analysis; D051996:Transcription Factor RelA; D014157:Transcription Factors / Q000037:antagonists & inhibitors; D014245:Trichomonas Infections / Q000276:immunology; D014246:Trichomonas vaginalis / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
chemical_list: D016207:Cytokines; D020672:I-kappa B Proteins; D016328:NF-kappa B; D052002:NF-kappa B p50 Subunit; C000606205:Nfkbia protein, mouse; D012333:RNA, Messenger; D051996:Transcription Factor RelA; D014157:Transcription Factors; D014409:Tumor Necrosis Factor-alpha; D000072000:NF-KappaB Inhibitor alpha; C073701:Nfkb1 protein, mouse; D018664:Interleukin-12