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Published on: December 21, 2011
Activation of MAPK Is Required for ROS Generation and Exocytosis in HMC-1 Cells Induced by Trichomonas
Giimaa Narantsogt1,2, Arim Min1, Young Hee Nam1
1Department of Environmental Medical Biology, Institute of Tropical Medicine, Yonsei University College of Medicine, Seoul 03722, Korea.
Abstract:
Trichomonas vaginalis is a flagellated protozoan parasite that causes vaginitis and cervicitis in women and asymptomatic urethritis and prostatitis in men. Mast cells have been reported to be predominant in vaginal smears and vaginal walls of patients infected with T. vaginalis. Mitogen-activated protein kinase (MAPK), activated by various stimuli, have been shown to regulate the transcriptional activity of various cytokine genes in mast cells. In this study, we investigated whether MAPK is involved in ROS generation and exocytotic degranulation in HMC-1 cells induced by T. vaginalis-derived secretory products (TvSP). We found that TvSP induces the activation of MAPK and NADPH oxidase in HMC-1 cells. Stimulation with TvSP induced phosphorylation of MAPK and p47(phox) in HMC-1 cells. Stimulation with TvSP also induced up-regulation of CD63, a marker for exocytosis, along the surfaces of human mast cells. Pretreatment with MAPK inhibitors strongly inhibited TvSP-induced ROS generation and exocytotic degranulation. Finally, our results suggest that TvSP induces intracellular ROS generation and exocytotic degranulation in HMC-1 via MAPK signaling.
Insights
Trichomonas vaginalis secretory products activate mast cells, causing reactive oxygen species (ROS) generation and degranulation. Mitogen-activated protein kinase (MAPK) signaling pathways mediate this response in human mast cells.
Area of Science:
- Immunology
- Parasitology
- Cell Biology
Background:
- Trichomonas vaginalis is a protozoan parasite causing urogenital infections.
- Mast cells are implicated in T. vaginalis infections, with their role in parasite-induced inflammation unclear.
- Mitogen-activated protein kinases (MAPK) regulate mast cell responses.
Purpose of the Study:
- To investigate the role of MAPK in mast cell activation by T. vaginalis secretory products (TvSP).
- To determine if MAPK signaling mediates reactive oxygen species (ROS) generation and degranulation in mast cells stimulated by TvSP.
Main Methods:
- Human mast cell line (HMC-1) stimulation with TvSP.
- Assessment of MAPK and NADPH oxidase activation (p47phox phosphorylation).
- Measurement of ROS generation and CD63 expression (exocytosis marker).
- Inhibition studies using MAPK inhibitors.
Main Results:
- TvSP activated MAPK and NADPH oxidase in HMC-1 cells.
- TvSP induced ROS generation and CD63 upregulation, indicating degranulation.
- MAPK inhibitors significantly reduced TvSP-induced ROS generation and degranulation.
- TvSP induced phosphorylation of MAPK and p47(phox).
Conclusions:
- TvSP triggers mast cell activation, including ROS production and degranulation.
- MAPK signaling pathways are crucial mediators of TvSP-induced mast cell responses.
- This study elucidates a key mechanism of mast cell involvement in T. vaginalis infections.
