title: Entamoeba histolytica-secreted cysteine proteases induce IL-8 production in human mast cells via a PAR2-independent mechanism.
abstract: 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.
authors: Department of Environmental Medical Biology, Institute of Tropical Medicine, and Brain Korea 21 Project for Medical Science, Yonsei University College of Medicine, Seoul 120-752, Korea.
authors: Young Ah
authors: YA
authors: Lee
authors: Department of Environmental Medical Biology, Institute of Tropical Medicine, and Brain Korea 21 Project for Medical Science, Yonsei University College of Medicine, Seoul 120-752, Korea.
authors: Young Hee
authors: YH
authors: Nam
authors: Department of Environmental Medical Biology, Institute of Tropical Medicine, and Brain Korea 21 Project for Medical Science, Yonsei University College of Medicine, Seoul 120-752, Korea.
authors: Arim
authors: A
authors: Min
authors: Department of Environmental Medical Biology, Institute of Tropical Medicine, and Brain Korea 21 Project for Medical Science, Yonsei University College of Medicine, Seoul 120-752, Korea.
authors: Kyeong Ah
authors: KA
authors: Kim
authors: Department of Parasitology, National Institute of Infectious Diseases, 1-23-1 Toyama, Shinjuku-ku, Tokyo, Japan.
authors: Tomoyoshi
authors: T
authors: Nozaki
authors: Department of Parasitology, National Institute of Infectious Diseases, 1-23-1 Toyama, Shinjuku-ku, Tokyo, Japan.
authors: Yumiko
authors: Y
authors: Saito-Nakano
authors: Department of Biological Chemistry, Weizmann Institute of Science, Rehovot 76100, Israel.
authors: David
authors: D
authors: Mirelman
authors: Department of Environmental Medical Biology, Institute of Tropical Medicine, and Brain Korea 21 Project for Medical Science, Yonsei University College of Medicine, Seoul 120-752, Korea.
authors: Myeong Heon
authors: MH
authors: Shin
mesh_terms: D000818:Animals; D015550:Cell Degranulation / Q000187:drug effects; D002460:Cell Line; D057056:Cysteine Proteases / Q000378:metabolism / Q000494:pharmacology* / Q000502:physiology; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D004748:Entamoeba histolytica / Q000201:enzymology* / Q000472:pathogenicity; D005089:Exocytosis; D006801:Humans; D016209:Interleukin-8 / Q000096:biosynthesis* / Q000235:genetics; D008407:Mast Cells / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D015800:Protozoan Proteins / Q000378:metabolism / Q000494:pharmacology* / Q000502:physiology; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D017382:Reactive Oxygen Species / Q000378:metabolism; D044464:Receptor, PAR-2 / Q000502:physiology; D014774:Virulence
chemical_list: D015853:Cysteine Proteinase Inhibitors; D016209:Interleukin-8; D015800:Protozoan Proteins; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D044464:Receptor, PAR-2; D057056:Cysteine Proteases