CoChat
Sign Up
Cited by 59Parasites and Host InteractionsInflammatory Bowel DiseaseHelminth infection and control

Parasitic Helminth Cystatin Inhibits DSS-Induced Intestinal Inflammation Via IL-10+F4/80+Macrophage Recruitment

Open access
Jang, Sung Won, Cho, Min Kyoung, Park, Mi Kyung, Kang, Shin Ae, Na, Byoung-Kuk, Ahn, Soon Cheol, Kim, Dong-Hee, Yu, Hak Sun·2011·The Korean Journal of Parasitology
DOI 10.3347/kjp.2011.49.3.245PMC PMC3210841
Open this paper in CoChat — free accountOpen PDF

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.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.3347/kjp.2011.49.3.245

Cites

1 of 1 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Helminth cystatins from S. japonicum, Ascaris lumbricoides, and Clonorchis sinensis all ameliorate colitis in vivo.

    “Other helminth cystatins with broad immunomodulatory properties including those from S. japonicum (Wang et al., 2016), Ascaris lumbricoides, and the liver fluke Clonorchis sinensis all ameliorate colitis in vivo”

    From Modulation of Host Immunity by Helminths: The Expanding Repertoire of Parasite Effector Molecules (2018) · cites this paper as Jang et al., 2011

    The Results section reports that recombinant CsStefin-1 from Clonorchis sinensis reduced disease activity and tissue damage in mice with DSS-induced colitis. Our copy does not report that cystatins from Ascaris lumbricoides or S. japonicum ameliorate colitis in vivo; the citing sentence separately cites Wang et al. (2016) for S. japonicum. Page numbers are unavailable in our copy. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

Research works printed but not linked: 42

  1. [1]Wang LJ Cao Y Shi HN Helminth infections and intestinal inflammation World J Gastroenterol 2008 14 5125 5132 18777588 PMC2744001
  2. [2]Magen E Borkow G Bentwich Z Mishal J Scharf S Can worms defend our hearts? Chronic helminthic infections may attenuate the development of cardiovascular diseases Med Hypotheses 2005 64 904 909 15780483
  3. [3]Fleming JO Cook TD Multiple sclerosis and the hygiene hypothesis Neurology 2006 67 2085 2086 17159130
  4. [4]Cooke A Zaccone P Raine T Phillips JM Dunne DW Infection and autoimmunity: Are we winning the war, only to lose the peace? Trends Parasitol 2004 20 316 321 15193562
  5. [5]Yang J Zhao J Yang Y Zhang L Yang X Zhu X Ji M Sun N Su C Schistosoma japonicum egg antigens stimulate CD4 CD25 T cells and modulate airway inflammation in a murine model of asthma Immunology 2007 120 8 18 17042799 PMC1890919
  6. [6]Akiho H Blennerhassett P Deng Y Collins SM Role of IL-4, IL-13, and STAT6 in inflammation-induced hypercontractility of murine smooth muscle cells Am J Physiol Gastrointest Liver Physiol 2002 282 G226 G232 11804843
  7. [7]Feillet H Bach JF Increased incidence of inflammatory bowel disease: The price of the decline of infectious burden? Curr Opin Gastroenterol 2004 20 560 564 15703683
  8. [9]Weinstock JV Summers RW Elliott DE Role of helminths in regulating mucosal inflammation Springer Semin Immunopathol 2005 27 249 271 15959781
  9. [10]Summers RW Elliott DE Urban JF Thompson R Weinstock JV Jr Trichuris suis therapy in Crohn's disease Gut 2005 54 87 90 15591509 PMC1774382
  10. [11]Elliott DE Urban JJ Argo CK Weinstock JV Does the failure to acquire helminthic parasites predispose to Crohn's disease? Faseb J 2000 14 1848 1855 10973934
  11. [12]Reardon C Sanchez A Hogaboam CM McKay DM Tapeworm infection reduces epithelial ion transport abnormalities in murine dextran sulfate sodium-induced colitis Infect Immun 2001 69 4417 4423 11401981 PMC98514
  12. [13]Khan WI Blennerhasset PA Varghese AK Chowdhury SK Omsted P Deng Y Collins SM Intestinal nematode infection ameliorates experimental colitis in mice Infect Immun 2002 70 5931 5937 12379667 PMC130294
  13. [14]Gregory WF Blaxter ML Maizels RM Differentially expressed, abundant trans-spliced cDNAs from larval Brugia malayi Mol Biochem Parasitol 1997 87 85 95 9233676
  14. [15]Park SK Cho MK Park HK Lee KH Lee SJ Choi SH Ock MS Jeong HJ Lee MH Yu HS Macrophage migration inhibitory factor homologs of Anisakis simplex suppress Th2 response in allergic airway inflammation model via CD4+CD25+Foxp3+ T cell recruitment J Immunol 2009 182 6907 6914 19454687
  15. [16]Yenbutr P Scott AL Molecular cloning of a serine proteinase inhibitor from Brugia malayi Infect Immun 1995 63 1745 1753 7729881 PMC173219
  16. [17]Murray J Gregory WF Gomez-Escobar N Atmadja AK Maizels RM Expression and immune recognition of Brugia malayi VAL-1, a homologue of vespid venom allergens and Ancylostoma secreted proteins Mol Biochem Parasitol 2001 118 89 96 11704277
  17. [18]Vray B Hartmann S Hoebeke J Immunomodulatory properties of cystatins Cell Mol Life Sci 2002 59 1503 1512 12440772 PMC11337455
  18. [19]Zavasnik-Bergant T Repnik U Schweiger A Romih R Jeras M Turk V Kos J Differentiation- and maturation-dependent content, localization, and secretion of cystatin C in human dendritic cells J Leukoc Biol 2005 78 122 134 15829557
  19. [20]Chapman HA Jr Reilly JJ Jr Yee R Grubb A Identification of cystatin C, a cysteine proteinase inhibitor, as a major secretory product of human alveolar macrophages in vitro Am Rev Respir Dis 1990 141 698 705 2310099
  20. [21]Murray J Manoury B Balic A Watts C Maizels RM 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 2005 139 197 203 15664654
  21. [22]Manoury B Gregory WF Maizels RM Watts C Bm-CPI-2, a cystatin homolog secreted by the filarial parasite Brugia malayi, inhibits class II MHC-restricted antigen processing Curr Biol 2001 11 447 451 11301256
  22. [23]Schonemeyer A Lucius R Sonnenburg B Brattig N Sabat R Schilling K Bradley J Hartmann S Modulation of human T cell responses and macrophage functions by onchocystatin, a secreted protein of the filarial nematode Onchocerca volvulus J Immunol 2001 167 3207 3215 11544307
  23. [24]Klotz C Ziegler T Figueiredo AS Rausch S Hepworth MR Obsivac N Sers C Lang R Hammerstein P Lucius R Hartmann S A helminth immunomodulator exploits host signaling events to regulate cytokine production in macrophages PLoS Pathog 2011 7 e1001248 21253577 PMC3017123
  24. [25]Schnoeller C Rausch S Pillai S Avagyan A Wittig BM Loddenkemper C Hamann A Hamelmann E Lucius R Hartmann S A helminth immunomodulator reduces allergic and inflammatory responses by induction of IL-10-producing macrophages J Immunol 2008 180 4265 4272 18322239
  25. [26]Tarasuk M Vichasri Grams S Viyanant V Grams R Type I cystatin(stefin) is a major component of Fasciola gigantica excretion/secretion product Mol Biochem Parasitol 2009 167 60 71 19416741
  26. [27]Kang JM Lee KH Sohn WM Na BK Identification and functional characterization of CsStefin-1, a cysteine protease inhibitor of Clonorchis sinensis Mol Biochem Parasitol 2011 177 126 134 21354219
  27. [28]Jeong YI Kim SH Ju JW Cho SH Lee WJ Park JW Park YM Lee SE 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 2011 407 793 800 21440530
  28. [29]Kim JY Cho MK Choi SH Lee KH Ahn SC Kim DH Yu HS 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 Mol Biochem Parasitol 2010 174 53 61 20603157
  29. [30]van Meeteren ME van Bergeijk JD van Dijk AP Tak CJ Meijssen MA Zijlstra FJ Intestinal permeability and contractility in murine colitis Mediators Inflamm 1998 7 163 168 9705603 PMC1781840
  30. [31]Kamada N Hisamatsu T Okamoto S Chinen H Kobayashi T Sato T Sakuraba A Kitazume MT Sugita A Koganei K Akagawa KS Hibi T Unique CD14 intestinal macrophages contribute to the pathogenesis of Crohn disease via IL-23/IFN-gamma axis J Clin Invest 2008 118 2269 2280 18497880 PMC2391067
  31. [32]Rogler G Hausmann M Vogl D Aschenbrenner E Andus T Falk W Andreesen R Scholmerich J Gross V Isolation and phenotypic characterization of colonic macrophages Clin Exp Immunol 1998 112 205 215 9649182 PMC1904962
  32. [33]Vitorino R Lobo MJ Ferrer-Correira AJ Dubin JR Tomer KB Domingues PM Amado FM Identification of human whole saliva protein components using proteomics Proteomics 2004 4 1109 1115 15048992
  33. [34]Di Quinzio MK Oliva K Holdsworth SJ Ayhan M Walker SP Rice GE Georgiou HM Permezel M Proteomic analysis and characterisation of human cervico-vaginal fluid proteins Aust N Z J Obstet Gynaecol 2007 47 9 15 17261093
  34. [35]Manoury B Hewitt EW Morrice N Dando PM Barrett AJ Watts C An asparaginyl endopeptidase processes a microbial antigen for class II MHC presentation Nature 1998 396 695 699 9872320
  35. [36]Owczarek D Cibor D Szczepanek M Mach T Biological therapy of inflammatory bowel disease Pol Arch Med Wewn 2009 119 84 88 19341184
  36. [37]Fiorino G Cesarini M Danese S Biological therapy for ulcerative colitis: What is after anti-TNF Curr Drug Targets 2011 12 1433 1439 21466492
  37. [38]Hoentjen F van Bodegraven AA Safety of anti-tumor necrosis factor therapy in inflammatory bowel disease World J Gastroenterol 2009 15 2067 2073 19418577 PMC2678575
  38. [39]Stallmach A Hagel S Bruns T Adverse effects of biologics used for treating IBD Best Pract Res Clin Gastroenterol 2010 24 167 182 20227030
  39. [40]Akbari O DeKruyff RH Umetsu DT Pulmonary dendritic cells producing IL-10 mediate tolerance induced by respiratory exposure to antigen Nat Immunol 2001 2 725 731 11477409
  40. [41]Saraiva M O'Garra A The regulation of IL-10 production by immune cells Nat Rev Immunol 2010 10 170 181 20154735
  41. [42]Presser K Schwinge D Wegmann M Huber S Schmitt S Quaas A Maxeiner JH Finotto S Lohse AW Blessing M Schramm C Coexpression of TGF-beta1 and IL-10 enables regulatory T cells to completely suppress airway hyperreactivity J Immunol 2008 181 7751 7758 19017964
  42. [43]Mottet C Uhlig HH Powrie F Cutting edge: Cure of colitis by CD4+CD25+ regulatory T cells J Immunol 2003 170 3939 3943 12682220

Cited by

Sorted by citations

Authors
Jang, S. W., Cho, M. K., Park, M. K., Kang, S. A., Na, B.-K., Ahn, S. C., Kim, D.-H., & Yu, H. S.
Affiliations
  • Pusan National University (KR)
  • Gyeongsang National University (KR)
Corresponding author
Yu, Hak Sun
ORCID
Venue
The Korean Journal of Parasitology
Publisher
Korean Society for Parasitology
Published
2011
Volume
49
Issue
3
Pages
245
ISSN
0023-4001 (ISSN-L)
DOI
10.3347/kjp.2011.49.3.245
PMC
PMC3210841
OpenAlex
W2034000325
Cited by
59
References
1
Citations by year
2026: 2 · 2025: 3 · 2024: 3 · 2023: 3 · 2022: 3 · 2021: 3 · 2020: 7 · 2019: 6 · 2018: 7 · 2017: 6 · 2016: 3 · 2015: 4 · 2014: 6 · 2013: 2 · 2012: 1
FWCI
2.02
Type
journal article
Language
en
Open access
Licence
cc-by-nc
Locations
  • Korean Journal of Parasitology (publishedVersion, cc-by-nc)
  • PubMed Central (publishedVersion, cc-by-nc)
  • PubMed (publishedVersion)
Funders
Pusan National University (PNU-2008-101-207)
Topics
  • Life Sciences › Immunology and Microbiology › Parasitology › Parasites and Host Interactions
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Inflammatory Bowel Disease
  • Health Sciences › Veterinary › Small Animals › Helminth infection and control
Keywords
cystatin, Clonorchis sinensis, intestinal inflammation, DSS-induced colitis, IL-10, F4/80+ macrophages, macrophage recruitment, immunomodulation, TNF-α, interferon-gamma, host-parasite interactions, liver fluke
MeSH terms
Animals, Antigens, Differentiation, Clonorchis sinensis, Colon, Female, Immunologic Factors, Inflammation, Intestines, Lymph Nodes, Macrophages, Mice, Inbred C57BL, Severity of Illness Index, Spleen, Helminth Proteins, Cystatins, Cytokines, Dextran Sulfate, Interleukin-10, Mice

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review