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

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          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.

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          Most cited references24

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          A new medium for the axenic cultivation of Entamoeba histolytica and other Entamoeba.

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            Toll-like receptors in the pathogenesis of human disease.

            Members of the Toll-like receptor (TLR) family are key regulators of both innate and adaptive immune responses. The function of TLRs in various human diseases has been investigated by comparison of the incidence of disease among people having different polymorphisms in genes that participate in TLR signaling. These studies have shown that TLR function affects several diseases, including sepsis, immunodeficiencies, atherosclerosis and asthma. As this body of data grows, it will provide new insights into disease pathogenesis as well as valuable information on the merits of various therapeutic options.
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              Endogenous ligands of Toll-like receptors: implications for regulating inflammatory and immune responses.

              A. Beg (2002)
              Toll-like receptors (TLRs) have a crucial role in regulating immunity against microbial agents. Recent studies indicate that these receptors might also have an important role in regulating responses to endogenous stimuli, such as necrotic cells, heat-shock proteins and extracellular matrix breakdown products. Specifically, TLR2 and TLR4 were shown to mediate expression of inflammatory genes and trigger dendritic-cell 'maturation' by these agents. These intriguing findings suggest that the ancient family of TLRs are involved in the recognition, not only of microbes, but also of endogenous harmful stimuli. However, potential complications associated with microbial contamination of endogenous agents and the specific nature of in vivo responses induced by these agents remain to be determined.
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                Author and article information

                Journal
                Parasite
                Parasite
                EDP Sciences
                1776-1042
                2014
                February 2014
                : 21
                :
                : 1
                Article
                10.1051/parasite/2014001
                b9b2e84e-49cb-4b57-a341-e3b50eb32671
                © 2014

                This work is licensed under a Creative Commons Attribution 4.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/

                History

                Parasitology,Life sciences
                Parasitology, Life sciences

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