CysLT receptor-mediated NOX2 activation is required for IL-8 production in HMC-1 cells induced by Trichomonas vaginalis-derived secretory products
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초록
Trichomoniasis is caused by a sexually transmitted flagellate protozoan parasite Trichomonas vaginalis. T. vaginalis-derived secretory products (TvSP) contain lipid mediators such as leukotriene B4 (LTB4) and various cysteinyl leukotrienes (CysLTs) which included LTC4, LTD4, and LTE4. However, the signaling mechanisms by which T. vaginalis-induced CysLTs stimulate interleukin (IL)-8 production in human mast cells remain unclear. In this study, we investigated these mechanisms in human mast cells (HMC-1). Stimulation with TvSP resulted in increased intracellular reactive oxygen species (ROS) generation and NADPH oxidase 2 (NOX2) activation compared to unstimulated cells. Pre-treatment with NOX2 inhibitors such as diphenyleneiodonium chloride (DPI) or apocynin significantly reduced ROS production in TvSP-stimulated HMC-1 cells. Additionally, TvSP stimulation increased NOX2 protein expression and the translocation of p47phox from the cytosol to the membrane. Pretreatment of HMC-1 cells with PI3K or PKC inhibitors reduced TvSP-induced p47phox translocation and ROS generation. Furthermore, NOX2 inhibitors or NOX2 siRNA prevented CREB phosphorylation and IL-8 gene expression or protein secretion induced by TvSP. Pretreatment with a CysLTR antagonist significantly inhibited TvSP-induced ROS production, CREB phosphorylation, and IL-8 production. These results indicate that CysLT-mediated activation of NOX2 plays a crucial role in ROS-dependent IL-8 production in human mast cells stimulated by T. vaginalis-secreted CysLTs. These findings enhance our understanding of the inflammatory response in trichomoniasis and may inform the development of targeted therapies to mitigate this response.
Abstract
Trichomoniasis is caused by a sexually transmitted flagellate protozoan parasite Trichomonas vaginalis. T. vaginalis-derived secretory products (TvSP) contain lipid mediators such as leukotriene B4 (LTB4) and various cysteinyl leukotrienes (CysLTs) which included LTC4, LTD4, and LTE4. However, the signaling mechanisms by which T. vaginalis-induced CysLTs stimulate interleukin (IL)-8 production in human mast cells remain unclear. In this study, we investigated these mechanisms in human mast cells (HMC-1). Stimulation with TvSP resulted in increased intracellular reactive oxygen species (ROS) generation and NADPH oxidase 2 (NOX2) activation compared to unstimulated cells. Pre-treatment with NOX2 inhibitors such as diphenyleneiodonium chloride (DPI) or apocynin significantly reduced ROS production in TvSP-stimulated HMC-1 cells. Additionally, TvSP stimulation increased NOX2 protein expression and the translocation of p47phox from the cytosol to the membrane. Pretreatment of HMC-1 cells with PI3K or PKC inhibitors reduced TvSP-induced p47phox translocation and ROS generation. Furthermore, NOX2 inhibitors or NOX2 siRNA prevented CREB phosphorylation and IL-8 gene expression or protein secretion induced by TvSP. Pretreatment with a CysLTR antagonist significantly inhibited TvSP-induced ROS production, CREB phosphorylation, and IL-8 production. These results indicate that CysLT-mediated activation of NOX2 plays a crucial role in ROS-dependent IL-8 production in human mast cells stimulated by T. vaginalis-secreted CysLTs. These findings enhance our understanding of the inflammatory response in trichomoniasis and may inform the development of targeted therapies to mitigate this response.
참고문헌 (28)
- Kobayashi TK, "Association of mast cells with vaginal trichomoniasis in endocervical smears", Acta Cytol, 27(2), pp.133~137 (1983)
- Kim HS, "Recent advances in mast cell activation and regulation", F1000Res, 9, pp.F1000 Faculty Rev-196~ (2020)[DOI]
- Mukai K, "Mast cells as sources of cytokines, chemokines, and growth factors", Immunol Rev, 282, pp.121~150 (2018)[DOI]
- Matsushima K, "Interleukin-8 : an evolving chemokine", Cytokine, 153, pp.155828~ (2022)[DOI]
- Mercer F, "Trichomonas vaginalis : pathogenesis, symbiont interactions, and host cell immune responses", Trends Parasitol, 34(8), pp.683~693 (2018)[DOI]
- Han IH, "Inflammatory response to Trichomonas vaginalis in the pathogenesis of prostatitis and benign prostatic hyperplasia", Parasites Hosts Dis, 61(1), pp.2~14 (2023)[DOI]
- Kummer S, "Induction of human host cell apoptosis by Trichomonas vaginalis cysteine proteases is modulated by parasite exposure to iron", Microb Pathog, 44(3), pp.197~203 (2008)[DOI]
- Szempruch AJ, "Sending a message : extracellular vesicles of pathogenic protozoan parasites", Nat Rev Microbiol, 14(11), pp.669~675 (2016)[DOI]
- Shaio MF, "A novel neutrophil-activating factor released by Trichomonas vaginalis", Infect Immun, 60(11), pp.4475~4482 (1992)[DOI]
- Nam YH, "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", Microbes Infect, 13(14-15), pp.1211~1220 (2011)[DOI]
- Lee YA, "Trichomonas vaginalissecreted cysteinyl leukotrienes promote migration, degranulation and MCP-1 production in mast cells", Parasite Immunol, 42(12), pp.e12789~ (2020)[DOI]
- Nam YH, "Leukotriene B(4)receptors BLT1 and BLT2 are involved in interleukin-8production in human neutrophils induced by Trichomonas vaginalis-derived secretory products", Inflamm Res, 61(2), pp.97~102 (2012)[DOI]
- Min A, "SNAP23-dependent surface translocation of leukotriene B4(LTB4)receptor 1 is essential for NOX2-mediated exocytotic degranulation in human mast cells induced by Trichomonas vaginalis-secreted LTB4", Infect Immun, 85(1), pp.e00526-16~ (2016)[DOI]
- Min A, "BLT1-mediated OGlcNAcylation is required for NOX2-dependent migration, exocytotic degranulation and IL-8 release of human mast cell induced by Trichomonas vaginalis-secreted LTB(4)", Microbes Infect, 20(6), pp.376~384 (2018)[DOI]
- Liu M, "The role of leukotrienes in allergic diseases", Allergol Int, 64(1), pp.17~26 (2015)[DOI]
- Kanaoka Y, "Roles of cysteinyl leukotrienes and their receptors in immune cell-related functions", Adv Immunol, 142, pp.65~84 (2019)[DOI]
- Kim KS, "Involvement of macrophages in proliferation of prostate cancer cells infected with Trichomonas vaginalis", Korean J Parasitol, 59(6), pp.557~564 (2021)[DOI]
- Cardamone C, "Mast cells as effector cells of innate immunity and regulators of adaptive immunity", Immunol Lett, 178, pp.10~14 (2016)[DOI]
- Lejeune M, "Prostaglandin E2 produced by Entamoeba histolytica signals via EP4 receptor and alters claudin-4 to increase ion permeability of tight junctions", Am J Pathol, 179(2), pp.807~818 (2011)[DOI]
- Angeli V, "Role of the parasite-derived prostaglandin D2 in the inhibition of epidermal Langerhans cell migration during schistosomiasis infection", J Exp Med, 193(10), pp.1135~1147 (2001)[DOI]
- Nam YH, "NF-кB and CREB are involved in IL-8 production of human neutrophils induced by Trichomonas vaginalis-derived secretory products", Korean J Parasitol, 49(3), pp.291~294 (2011)[DOI]
- Thompson C, "Signaling by the cysteinyl-leukotriene receptor 2. Involvement in chemokine gene transcription", J Biol Chem, 283(4), pp.1974~1984 (2008)[DOI]
- Thompson C, "CysLT1 receptor engagement induces activator protein-1-and NF-kappaB-dependent IL-8 expression", Am J Respir Cell Mol Biol, 35(6), pp.697~704 (2006)[DOI]
- Lin K, "ERK", Egr-1 signaling pathway is involved in CysLT2 receptor-mediated IL-8production in HEK293 cells, 2014, pp.93(7), 278~288
- Ichiyama T, "Pranlukast inhibits NF-kappa B activation in human monocytes", macrophages and T cells, 2003, pp.33(6), 802~827
- El-Benna J, "Priming of the neutrophil NADPH oxidase activation : role of p47phox phosphorylation and NOX2 mobilization to the plasma membrane", Semin Immunopathol, 30(3), pp.279~289 (2008)[DOI]
- Vermot A, "NADPH Oxidases(NOX) : an overview from discovery, molecular mechanisms to physiology and pathology", Antioxidants(Basel), 10(6), pp.890~ (2021)[DOI]
- Lee YA, "Involvement of NOX2-derived ROS in human hepatoma HepG2 cell death induced by Entamoeba histolytica", Parasites Hosts Dis, 61(4), pp.388~396 (2023)[DOI]