Proinflammatory Cytokine and Nitric Oxide Production by Human Macrophages Stimulated with Trichomonas vaginalis
Ik-Hwan Han,1Sung Young Goo,2Soon-Jung Park,2Se-Jin Hwang,3Yong-Seok Kim,4Michael Sungwoo Yang,5Myoung-Hee Ahn,1
and Jae-Sook Ryu1
1Department of Environmental Biology & Medical Parasitology, Hanyang University College of Medicine, Seoul 133-791, Korea.
2Department Environmental Medical Biology and Institute of Tropical Medicine, Brain Korea 21 Project, Yonsei University College of Medicine, Seoul 120-752, Korea.
3Department of Anatomy and Cell Biology, Hanyang University College of Medicine, Seoul 133-791, Korea.
4Department of Biochemistry and Molecular Biology, Hanyang University College of Medicine, Seoul 133-791, Korea.
5Indianhead International School, Uijeongbu 480-701, Korea.
Received June 28, 2009; Revised August 03, 2009; Accepted August 05, 2009.
Abstract
Trichomonas vaginalis commonly causes vaginitis and perhaps cervicitis in women and urethritis in men and women. Macrophages are important immune cells in response to T. vaginalis infection. In this study, we investigated whether human macrophages could be involved in inflammation induced by T. vaginalis. Human monocyte-derived macrophages (HMDM) were co-cultured with T. vaginalis. Live, opsonized-live trichomonads, and T. vaginalis lysates increased proinflammatory cytokines, such as TNF-α, IL-1β, and IL-6 by HMDM. The involvement of nuclear factor (NF)-κB signaling pathway in cytokine production induced by T. vaginalis was confirmed by phosphorylation and nuclear translocation of p65 NF-κB. In addition, stimulation with live T. vaginalis induced marked augmentation of nitric oxide (NO) production and expression of inducible NO synthase (iNOS) levels in HMDM. However, trichomonad-induced NF-κB activation and TNF-α production in macrophages were significantly inhibited by inhibition of iNOS levels with L-NMMA (NO synthase inhibitor). Moreover, pretreatment with NF-κB inhibitors (PDTC or Bay11-7082) caused human macrophages to produce less TNF-α. These results suggest that T. vaginalis stimulates human macrophages to produce proinflammatory cytokines, such as IL-1, IL-6, and TNF-α, and NO. In particular, we showed that T. vaginalis induced TNF-α production in macrophages through NO-dependent activation of NF-κB, which might be closely involved in inflammation caused by T. vaginalis.
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