Role of MAPK signaling on human mast cell activation induced by Trichomonas vaginalis / Шинэ санаа Шинэ нээлт

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 the vaginal smears and vaginal walls of patients infected with T. vaginalis. Mitogen activated protein kinase (MAPK) activated by various stimuli also regulate the transcriptional activity of various cytokine genes in the mast cells. Because of their essential role in intracellular signaling network, also appropriate targets for pharmacological treatment of inflammatory disorders.Cultivation of T.vaginalis and HMC-1 line, preparation of TvSP, to check intracellular ROS level and degranulation by FACS, to determine phosphorylation of MAPK and p47phox by immunobloting.In this study, we investigated whether MAPK were involved ROS generation and exocytotic degranulation in HMC-1 induced by T. vaginalis-derived secretory products (TvSP). We first examined that TvSP could induce activation of MAPK and NADPH oxidase in HMC-1 cells. Stimulation with TvSP induced phosphorylation of MAPK and p47phox in HMC-1 cells. Phosphorylation of p47phox is main source of ROS generation. Next, to determine involvement activation of MAPK in ROS generation and degranulation in HMC-1 cells induced by TvSP. ROS generation is required for exocytotic degranulation of mast cells induced by TvSP. Stimulation with TvSP induced phosphorylation of p47phox, ROSgeneration, and surface up-regulation of CD63 in human mast cells. CD63 is a marker for exocytosis. Pretreatment with MAPK inhibitors strongly inhibited TvSP-induced ROS generation and exocytotic degranulation.Our results suggest that TvSP could induce intracellular ROS generation and exocytotic degranulation in HMC-1 via MAPK signaling pathway.