leukotriene-b4 and Trichomonas-Infections

Trichomonas vaginalis is a flagellated protozoan parasite that causes human trichomoniasis. Although T. vaginalis itself can secrete lipid mediator leukotriene (LT) B(4) leading to neutrophil activation, information regarding the signaling mechanism involved in neutrophil activation induced by T. vaginalis-secreted LTB(4) is limited. We investigated whether LTB(4) contained in the T. vaginalis-derived secretory products (TvSP) is closely involved in interleukin (IL)-8 production in human neutrophils via LTB(4) receptors BLT1 or BLT2.. T. vaginalis produced more than 714 pg/ml of LTB(4) per 1 × 10(7) trichomonads. The ability of trichomonads to secrete LTB(4) was inhibited by treatment of trichomonads with the 5-lipo-oxygenease inhibitor AA861, but not the cyclo-oxygenease I inhibitor FR122047. When neutrophils were incubated with TvSP obtained from 1 × 10(7) trichomonads, IL-8 protein secretion was significantly increased compared to results for cells incubated with medium alone. The stimulatory effect of TvSP on IL-8 production was strongly inhibited by pretreatment of TvSP with lipase, although pretreatment with heat or proteinase K showed little inhibitory effect. Moreover, TvSP-induced IL-8 production was efficiently inhibited when trichomonads were pretreated with AA861 or when neutrophils were pretreated with antagonists for BLT1 or BLT2.. Our results suggest that LTB(4) receptors BLT1 and BLT2 are involved in IL-8 production in neutrophils induced by T. vaginalis.

Topics: Benzoquinones; Endopeptidase K; Fatty Alcohols; Glycols; Hot Temperature; Humans; Interleukin-8; Leukotriene Antagonists; Leukotriene B4; Lipase; Lipoxygenase Inhibitors; Neutrophil Activation; Neutrophils; Piperazines; Receptors, Leukotriene B4; Tetrazoles; Thiazoles; Trichomonas Infections; Trichomonas vaginalis

Trichomonas vaginalis is a protozoan parasite that causes acute tissue inflammation in vaginal trichomoniasis. In this study, we investigated the signaling mechanisms through which T. vaginalis-derived secretory products (TvSP) induce chemokine IL-8 production in human mast cells. Stimulation with TvSP induced up-regulation of IL-8 protein secretion in HMC-1 cells. In addition, TvSP induced phosphorylation of transcription factors NF-κB and CREB in HMC-1 cells. Pretreatment of TvSP with lipase, but not heat or proteinase K strongly abolished the stimulatory effect on IL-8 production. Moreover, TvSP-induced IL-8 production and phosphorylation of NF-κB or CREB were inhibited when HMC-1 cells were stimulated with modified TvSP collected from 5-lipooxygenase inhibitor-treated trichomonads. Indeed, T. vaginalis-secreted lipid mediator LTB(4) (700pg/ml) from 1×10(7) trichomonads. Furthermore, pretreatment of HMC-1 cells with antagonists for LTB(4) receptors BLT1 or BLT2 abolished the stimulatory effects of TvSP. Finally, TvSP-induced IL-8 production was inhibited by pretreatment with IκB or CREB inhibitors. These results suggest that T. vaginalis-derived secretory lipid mediator LTB(4) induces IL-8 production in mast cells via BLT-dependent activation of NF-κB and CREB.

Topics: Cells, Cultured; Culture Media, Conditioned; Cyclic AMP Response Element-Binding Protein; Cyclopentanes; Endopeptidase K; Female; Gene Expression Regulation; Hot Temperature; Humans; Interleukin-8; Leukotriene B4; Lipase; Mast Cells; NF-kappa B; Phosphorylation; Receptors, Cell Surface; Signal Transduction; Thiosemicarbazones; Transcription Factor RelA; Trichomonas Infections; Trichomonas vaginalis