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BLT1-mediated O-GlcNAcylation is required for NOX2-dependent migration, exocytotic degranulation and IL-8 release of human mast cell induced by Trichomonas vaginalis-secreted LTB4

 Arim Min  ;  Young Ah Lee  ;  Kyeong Ah Kim  ;  Myeong Heon Shin 
 Microbes and Infection, Vol.20(6) : 376-384, 2018 
Journal Title
 Microbes and Infection 
Issue Date
BLT1 ; Human mast cells ; Leukotriene B(4) ; NOX2 ; O-GlcNAcylation ; Trichomonas vaginalis
Trichomonas vaginalis is a sexually-transmitted protozoan parasite that causes vaginitis and cervicitis. Although mast cell activation is important for provoking tissue inflammation during infection with parasites, information regarding the signaling mechanisms in mast cell activation and T. vaginalis infection is limited. O-linked N-acetylglucosamine (O-GlcNAc) is a post-translational modification of serine and threonine residues that functions as a critical regulator of intracellular signaling, regulated by O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA). We investigated if O-GlcNAcylation was associated with mast cell activation induced by T. vaginalis-derived secretory products (TvSP). Modified TvSP collected from live trichomonads treated with the 5-lipooxygenase inhibitor AA861 inhibited migration of mast cells. This result suggested that mast cell migration was caused by stimulation of T. vaginalis-secreted leukotrienes. Using the BLT1 antagonist U75302 or BLT1 siRNA, we found that migration of mast cells was evoked via LTB4 receptor (BLT1). Furthermore, TvSP induced protein O-GlcNAcylation and OGT expression in HMC-1 cells, which was prevented by transfection with BLT1 siRNA. TvSP-induced migration, ROS generation, CD63 expression and IL-8 release were significantly suppressed by pretreatment with OGT inhibitor ST045849 or OGT siRNA. These results suggested that BLT1-mediated OGlcNAcylation was important for mast cell activation during trichomoniasis.
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1. Journal Papers (연구논문) > 1. College of Medicine (의과대학) > Dept. of Environmental Medical Biology (환경의생물학교실)
Yonsei Authors
민아림(Min, A Rim) ORCID logo https://orcid.org/0000-0003-2938-9630
신명헌(Shin, Myeong Heon) ORCID logo https://orcid.org/0000-0001-8207-6110
이영아(Lee, Young Ah) ORCID logo https://orcid.org/0000-0002-0414-842X
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