title: Leukotriene B4 receptor BLT-mediated phosphorylation of NF-κB and CREB is involved in IL-8 production in human mast cells induced by Trichomonas vaginalis-derived secretory products.
abstract: 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.
authors.affiliation: Department of Environmental Medical Biology, Yonsei University College of Medicine, 134 Sichon-dong, Seodaemun-gu, Seoul 120-752, Republic of Korea.
authors.forename: Young Hee
authors.initials: YH
authors.lastname: Nam
authors.forename: Deulle
authors.initials: D
authors.lastname: Min
authors.forename: Hyoung-Pyo
authors.initials: HP
authors.lastname: Kim
authors.forename: Kyoung-Ju
authors.initials: KJ
authors.lastname: Song
authors.forename: Kyeong Ah
authors.initials: KA
authors.lastname: Kim
authors.forename: Young Ah
authors.initials: YA
authors.lastname: Lee
authors.forename: Seong Hoon
authors.initials: SH
authors.lastname: Kim
authors.forename: Myeong Heon
authors.initials: MH
authors.lastname: Shin
mesh_terms: D002478:Cells, Cultured; D017077:Culture Media, Conditioned / Q000494:pharmacology; D017362:Cyclic AMP Response Element-Binding Protein / Q000037:antagonists & inhibitors / Q000276:immunology* / Q000378:metabolism; D003517:Cyclopentanes / Q000494:pharmacology; D019286:Endopeptidase K / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation / Q000276:immunology; D006358:Hot Temperature; D006801:Humans; D016209:Interleukin-8 / Q000096:biosynthesis / Q000276:immunology; D007975:Leukotriene B4 / Q000276:immunology / Q000378:metabolism / Q000494:pharmacology*; D008049:Lipase / Q000378:metabolism; D008407:Mast Cells / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000276:immunology* / Q000378:metabolism; D010766:Phosphorylation / Q000276:immunology; D011956:Receptors, Cell Surface / Q000037:antagonists & inhibitors / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology; D013882:Thiosemicarbazones / Q000494:pharmacology; D051996:Transcription Factor RelA / Q000037:antagonists & inhibitors / Q000276:immunology / Q000378:metabolism; D014245:Trichomonas Infections / Q000276:immunology* / Q000469:parasitology; D014246:Trichomonas vaginalis / Q000276:immunology* / Q000378:metabolism
chemical_list: C526651:2-hexyl-1-cyclopentanone thiosemicarbazone; C115163:CREB1 protein, human; D017077:Culture Media, Conditioned; D017362:Cyclic AMP Response Element-Binding Protein; D003517:Cyclopentanes; D016209:Interleukin-8; D016328:NF-kappa B; D011956:Receptors, Cell Surface; D013882:Thiosemicarbazones; D051996:Transcription Factor RelA; D007975:Leukotriene B4; D008049:Lipase; D019286:Endopeptidase K