Parasitic Helminth Cystatin Inhibits DSS-Induced Intestinal Inflammation Via IL-10^+F4/80^+ Macrophage Recruitment
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Many immune down-regulatory molecules have been isolated from parasites, including cystatin (cystain protease inhibitor). In a previous study, we isolated and characterized Type I cystatin (CsStefin-1) of the liver fluke, Clonorchis sinensis. To investigate whether the CsStefin-1 might be a new host immune modulator, we induced intestinal inflammation in mice by dextran sodium sulfate (DSS) and treated them with recombinant CsStefin-1 (rCsStefin-1). The disease activity index (DAI) increased in DSS only-treated mice. In contrast, the DAI value was significantly reduced in rCsStefin-1-treated mice than DSS only-treated mice. In addition, the colon length of DSS only-treated mice was shorter than that of rCsStefin-1 treated mice. The secretion levels of IFN-γ and TNF-α in the spleen and mesenteric lymph nodes (MLNs) were significantly increased by DSS treatment, but the level of TNF-α in MLNs was significantly decreased by rCsStefin-1 treatment. IL-10 production in both spleen and MLNs was significantly increased, and IL-10^+F4/80^+ macrophage cells were significantly increased in the spleen and MLNs of rCsStefin-1 treated mice after DSS treatment. In conclusion, rCsStefin-1 could reduce the intestinal inflammation occurring after DSS treatment, these effects might be related with recruitment of IL-10 secreting macrophages.
Abstract
Many immune down-regulatory molecules have been isolated from parasites, including cystatin (cystain protease inhibitor). In a previous study, we isolated and characterized Type I cystatin (CsStefin-1) of the liver fluke, Clonorchis sinensis. To investigate whether the CsStefin-1 might be a new host immune modulator, we induced intestinal inflammation in mice by dextran sodium sulfate (DSS) and treated them with recombinant CsStefin-1 (rCsStefin-1). The disease activity index (DAI) increased in DSS only-treated mice. In contrast, the DAI value was significantly reduced in rCsStefin-1-treated mice than DSS only-treated mice. In addition, the colon length of DSS only-treated mice was shorter than that of rCsStefin-1 treated mice. The secretion levels of IFN-γ and TNF-α in the spleen and mesenteric lymph nodes (MLNs) were significantly increased by DSS treatment, but the level of TNF-α in MLNs was significantly decreased by rCsStefin-1 treatment. IL-10 production in both spleen and MLNs was significantly increased, and IL-10^+F4/80^+ macrophage cells were significantly increased in the spleen and MLNs of rCsStefin-1 treated mice after DSS treatment. In conclusion, rCsStefin-1 could reduce the intestinal inflammation occurring after DSS treatment, these effects might be related with recruitment of IL-10 secreting macrophages.
참고문헌 (43)
- Wang LJ, "Helminth infections and intestinal inflammation", World J Gastroenterol, 14, pp.5125~5132 (2008)
- Magen E, "Can worms defend our hearts? Chronic helminthic infections may attenuate the development of cardiovascular diseases", Med Hypotheses, 64, pp.904~909 (2005)
- Fleming JO, "Multiple sclerosis and the hygiene hypothesis", Neurology, 67, pp.2085~2086 (2006)
- Cooke A, "Infection and autoimmunity: Are we winning the war, only to lose the peace", Trends Parasitol, 20, pp.316~321 (2004)
- Yang J, "Schistosoma japonicum egg antigens stimulate CD4 CD25 T cells and modulate airway inflammation in a murine model of asthma", Immunology, 120, pp.8~18 (2007)
- Akiho H, "Role of IL-4, IL-13, and STAT6 in inflammation-induced hypercontractility of murine smooth muscle cells", Am J Physiol Gastrointest Liver Physiol, 282, pp.226~232 (2002)
- Feillet H, "Increased incidence of inflammatory bowel disease: The price of the decline of infectious burden", Curr Opin Gastroenterol, 20, pp.560~564 (2004)
- Fiocchi C, "Inflammatory bowel disease: Etiology and pathogenesis", Gastroenterology, pp.182~205 (1998)
- Weinstock JV, "Role of helminths in regulating mucosal inflammation", Springer Semin Immunopathol, 27, pp.249~271 (2005)
- Summers RW, "suis therapy in Crohn’s disease", Gut, 54, pp.87~90 (2005)
- Elliott DE, "Does the failure to acquire helminthic parasites predispose to Crohn’s disease", Faseb J, 14, pp.1848~1855 (2000)
- Reardon C, "Tapeworm infection reduces epithelial ion transport abnormalities in murine dextran sulfate sodium-induced colitis", Infect Immun, 69, pp.4417~4423 (2001)
- Khan WI, "Intestinal nematode infection ameliorates experimental colitis in mice", Infect Immun, 70, pp.5931~5937 (2002)
- Gregory WF, "Differentially expressed, abundant trans-spliced cDNAs from larval Brugia malayi", Mol Biochem Parasitol, 87, pp.85~95 (1997)
- Park SK, "Macrophage Migration Inhibitory Factor Homologs of Anisakis simplex Suppress Th2 Response in Allergic Airway Inflammation Model via CD4(+)CD25(+)Foxp3(+) T Cell Recruitment", JOURNAL OF IMMUNOLOGY, 182(11), pp.6907~6914 (2009), AMER ASSOC IMMUNOLOGISTS
- Yenbutr P, "Molecular cloning of a serine proteinase inhibitor from Brugia malayi", Infect Immun, 63, pp.1745~1753 (1995)
- Murray J, "Expression and immune recognition of Brugia malayi VAL-1, a homologue of vespid venom allergens and Ancylostoma secreted proteins", Mol Biochem Parasitol, 118, pp.89~96 (2001)
- Vray B, "properties of cystatins", Cell Mol Life Sci, 59, pp.1503~1512 (2002)
- Zavasnik-Bergant T, "Differentiation- and maturation-dependent content, localization, and secretion of cystatin C in human dendritic cells", J Leukoc Biol, 78, pp.122~134 (2005)
- Chapman HA Jr, "Identification of cystatin C, a cysteine proteinase inhibitor, as a major secretory product of human alveolar macrophages in vitro", Am Rev Respir Dis, 141, pp.698~705 (1990)
- Murray J, "Bm-CPI-2, a cystatin from Brugia malayi nematode parasites, differs from Caenorhabditis elegans cystatins in a specific site mediating inhibition of the antigen-processing enzyme AEP", Mol Biochem Parasitol, 139, pp.197~203 (2005)
- Manoury B, "Bm-CPI-2, a cystatin homolog secreted by the filarial parasite Brugia malayi, inhibits class II MHC-restricted antigen processing", Curr Biol, 11, pp.447~451 (2001)
- Schonemeyer A, "Modulation of human T cell responses and macrophage functions by onchocystatin, a secreted protein of the filarial nematode Onchocerca volvulus", J Immunol, 167, pp.3207~3215 (2001)
- Klotz C, "A helminth immunomodulator exploits host signaling events to regulate cytokine production in macrophages", PLoS Pathog, 7, pp.1001248~ (2011)
- Schnoeller C, "A helminth immunomodulator reduces allergic and inflammatory responses by induction of IL-10-producing macrophages", J Immunol, 180, pp.4265~4272 (2008)
- Tarasuk M, "Type I cystatin (stefin) is a major component of Fasciola gigantica excretion", secretion product, 2009, pp.167, 60~71
- Kang JM, "Identification and functional characterization of CsStefin-1, a cysteine protease inhibitor of Clonorchis sinensis", MOLECULAR AND BIOCHEMICAL PARASITOLOGY, 177(2), pp.126~134 (2011), ELSEVIER SCIENCE BV
- Jeong YI, "Clonorchis sinensis-derived total protein attenuates airway inflammation in murine asthma model by inducing regulatory T cells and modulating dendritic cell functions", Biochem Biophys Res Commun, 407, pp.793~800 (2011)
- Kim JY, "Inhibition of dextran sulfate sodium (DSS)-induced intestinal inflammation via enhanced IL-10 and TGF-beta production by galectin-9 homologues isolated from intestinal parasites", MOLECULAR AND BIOCHEMICAL PARASITOLOGY, 174, pp.53~61 (2010), Blackwell Publishing Ltd
- van Meeteren ME, "Intestinal permeability and contractility in murine colitis", Mediators Inflamm, 7, pp.163~168 (1998)
- Kamada N, "Akagawa KS, Hibi T. Unique CD14 intestinal macrophages contribute to the pathogenesis of Crohn disease via IL-23", IFN-gamma axis, 2008, pp.118, 2269~2280
- Rogler G, "Isolation and phenotypic characterization of colonic macrophages", Clin Exp Immunol, 112, pp.205~215 (1998)
- Vitorino R, "Identification of human whole saliva protein components using proteomics", Proteomics, 4, pp.1109~1115 (2004)
- Di Quinzio MK, "Proteomic analysis and characterisation of human cervico-vaginal fluid proteins", Aust N Z J Obstet Gynaecol, 47, pp.9~15 (2007)
- Manoury B, "An asparaginyl endopeptidase processes a microbial antigen for class II MHC presentation", Nature, 396, pp.695~699 (1998)
- Owczarek D, "Biological therapy of inflammatory bowel disease", Pol Arch Med Wewn, 119, pp.84~88 (2009)
- Fiorino G, "Biological therapy for ulcerative colitis: What is after anti-TNF", Curr Drug Targets, 12, pp.1433~1439 (2011)
- Hoentjen F, "Safety of anti-tumor necrosis factor therapy in inflammatory bowel disease", World J Gastroenterol, 15, pp.2067~2073 (2009)
- Stallmach A, "Adverse effects of biologics used for treating IBD", Best Pract Res Clin Gastroenterol, 24, pp.167~182 (2010)
- Akbari O, "Pulmonary dendritic cells producing IL-10 mediate tolerance induced by respiratory exposure to antigen", Nat Immunol, 2, pp.725~731 (2001)
- Saraiva M, "The regulation of IL-10 production by immune cell", Nat Rev Immunol, 10, pp.170~181 (2010)
- Presser K, "Coexpression of TGF-beta1 and IL-10 enables regulatory T cells to completely suppress airway hyperreactivity", J Immunol, 181, pp.7751~7758 (2008)
- Mottet C, "Cutting edge: Cure of colitis by CD4+CD25+ regulatory T cells", J Immunol, 170, pp.3939~3943 (2003)