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Entamoeba histolytica-secreted cysteine proteases induce IL-8 production in human mast cells via a PAR2-independent mechanism

 Young Ah Lee  ;  Young Hee Nam  ;  Arim Min  ;  Kyeong Ah Kim  ;  Tomoyoshi Nozaki  ;  Yumiko Saito-Nakano  ;  David Mirelman  ;  Myeong Heon Shin 
 PARASITE, Vol.21(1) : 1-9, 2014 
Journal Title
Issue Date
Animals ; Cell Degranulation/drug effects ; Cell Line ; Cysteine Proteases/pharmacology* ; Cysteine Proteases/physiology ; Cysteine Proteases/secretion ; Cysteine Proteinase Inhibitors/pharmacology ; Entamoeba histolytica/enzymology* ; Entamoeba histolytica/pathogenicity ; Exocytosis ; Humans ; Interleukin-8/biosynthesis* ; Interleukin-8/genetics ; Mast Cells/drug effects* ; Mast Cells/metabolism ; Mice ; Mice, Inbred BALB C ; Protozoan Proteins/pharmacology* ; Protozoan Proteins/physiology ; Protozoan Proteins/secretion ; RNA, Messenger/biosynthesis ; RNA, Messenger/genetics ; Reactive Oxygen Species/metabolism ; Receptor, PAR-2/physiology ; Virulence
Entamoeba histolytica ; Cysteine protease ; Mast cell ; IL-8 ; Protease-activated receptor 2 (PAR2)
Entamoeba histolytica is an extracellular tissue parasite causing colitis and occasional liver abscess in humans. E. histolytica-derived secretory products (SPs) contain large amounts of cysteine proteases (CPs), one of the important amoebic virulence factors. Although tissue-residing mast cells play an important role in the mucosal inflammatory response to this pathogen, it is not known whether the SPs induce mast cell activation. In this study, when human mast cells (HMC-1 cells) were stimulated with SPs collected from pathogenic wild-type amoebae, interleukin IL-8 mRNA expression and production were significantly increased compared with cells incubated with medium alone. Inhibition of CP activity in the SPs with heat or the CP inhibitor E64 resulted in significant reduction of IL-8 production. Moreover, SPs obtained from inhibitors of cysteine protease (ICP)-overexpressing amoebae with low CP activity showed weaker stimulatory effects on IL-8 production than the wild-type control. Preincubation of HMC-1 cells with antibodies to human protease-activated receptor 2 (PAR2) did not affect the SP-induced IL-8 production. These results suggest that cysteine proteases in E. histolytica-derived secretory products stimulate mast cells to produce IL-8 via a PAR2-independent mechanism, which contributes to IL-8-mediated tissue inflammatory responses during the early phase of human amoebiasis.
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1. College of Medicine (의과대학) > Dept. of Tropica Medicine (열대의학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Yonsei Biomedical Research Center (연세의생명연구원) > 1. Journal Papers
Yonsei Authors
Kim, Kyung Ah(김경아)
Nam, Young Hee(남영희)
Min, A Rim(민아림) ORCID logo https://orcid.org/0000-0003-2938-9630
Shin, Myeong Heon(신명헌) ORCID logo https://orcid.org/0000-0001-8207-6110
Lee, Young Ah(이영아) ORCID logo https://orcid.org/0000-0002-0414-842X
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