Proinflammatory cytokine and nitric oxide production by human macrophages stimulated with Trichomonas vaginalis.
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-alpha, IL-1beta, and IL-6 by HMDM. The involvement of nuclear factor (NF)-kappaB signaling pathway in cytokine production induced by T. vaginalis was confirmed by phosphorylation and nuclear translocation of p65 NF-kappaB. 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-kappaB activation and TNF-alpha production in macrophages were significantly inhibited by inhibition of iNOS levels with L-NMMA (NO synthase inhibitor). Moreover, pretreatment with NF-kappaB inhibitors (PDTC or Bay11-7082) caused human macrophages to produce less TNF-alpha. These results suggest that T. vaginalis stimulates human macrophages to produce proinflammatory cytokines, such as IL-1, IL-6, and TNF-alpha, and NO. In particular, we showed that T. vaginalis induced TNF-alpha production in macrophages through NO-dependent activation of NF-kappaB, which might be closely involved in inflammation caused by T. vaginalis.
Han
Ik-Hwan
IH
Department of Environmental Biology & Medical Parasitology, Hanyang University College of Medicine, Seoul, Korea.
Goo
Sung Young
SY
Park
Soon-Jung
SJ
Hwang
Se-Jin
SJ
Kim
Yong-Seok
YS
Yang
Michael Sungwoo
MS
Ahn
Myoung-Hee
MH
Ryu
Jae-Sook
JS
D000818:Animals; D002478:Cells, Cultured; D016207:Cytokines / Q000276:immunology*; D006801:Humans; D008264:Macrophages / Q000276:immunology* / Q000469:parasitology; D009569:Nitric Oxide / Q000276:immunology*; D014245:Trichomonas Infections / Q000276:immunology* / Q000469:parasitology; D014246:Trichomonas vaginalis / Q000276:immunology*
D016207:Cytokines; D009569:Nitric Oxide