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  1. Article: The Effect of a Novel Serine Protease Inhibitor on Inflammation and Intestinal Permeability in a Murine Colitis Transfer Model.

    Van Spaendonk, Hanne / Ceuleers, Hannah / Smet, Annemieke / Berg, Maya / Joossens, Jurgen / Van der Veken, Pieter / Francque, Sven M / Lambeir, Anne-Marie / De Man, Joris G / De Meester, Ingrid / Augustyns, Koen / De Winter, Benedicte Y

    Frontiers in pharmacology

    2021  Volume 12, Page(s) 682065

    Abstract: Background: ...

    Abstract Background:
    Language English
    Publishing date 2021-06-24
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2587355-6
    ISSN 1663-9812
    ISSN 1663-9812
    DOI 10.3389/fphar.2021.682065
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: In-Depth Study of Transmembrane Mucins in Association with Intestinal Barrier Dysfunction During the Course of T Cell Transfer and DSS-Induced Colitis.

    Breugelmans, Tom / Van Spaendonk, Hanne / De Man, Joris G / De Schepper, Heiko U / Jauregui-Amezaga, Aranzazu / Macken, Elisabeth / Lindén, Sara K / Pintelon, Isabel / Timmermans, Jean-Pierre / De Winter, Benedicte Y / Smet, Annemieke

    Journal of Crohn's & colitis

    2020  Volume 14, Issue 7, Page(s) 974–994

    Abstract: Background and aims: There is evidence for a disturbed intestinal barrier function in inflammatory bowel diseases [IBD] but the underlying mechanisms are unclear. Because mucins represent the major components of the mucus barrier and disturbed mucin ... ...

    Abstract Background and aims: There is evidence for a disturbed intestinal barrier function in inflammatory bowel diseases [IBD] but the underlying mechanisms are unclear. Because mucins represent the major components of the mucus barrier and disturbed mucin expression is reported in the colon of IBD patients, we studied the association between mucin expression, inflammation and intestinal permeability in experimental colitis.
    Methods: We quantified 4-kDa FITC-dextran intestinal permeability and the expression of cytokines, mucins, junctional and polarity proteins at dedicated time points in the adoptive T cell transfer and dextran sodium sulfate [DSS]-induced colitis models. Mucin expression was also validated in biopsies from IBD patients.
    Results: In both animal models, the course of colitis was associated with increased interleukin-1β [IL-1β] and tumour necrosis factor-α [TNF-α] expression and increased Muc1 and Muc13 expression. In the T cell transfer model, a gradually increasing Muc1 expression coincided with gradually increasing 4-kDa FITC-dextran intestinal permeability and correlated with enhanced IL-1β expression. In the DSS model, Muc13 expression coincided with rapidly increased 4-kDa FITC-dextran intestinal permeability and correlated with TNF-α and Muc1 overexpression. Moreover, a significant association was observed between Muc1, Cldn1, Ocln, Par3 and aPKCζ expression in the T cell transfer model and between Muc13, Cldn1, Jam2, Tjp2, aPkcζ, Crb3 and Scrib expression in the DSS model. Additionally, MUC1 and MUC13 expression was upregulated in inflamed mucosa of IBD patients.
    Conclusions: Aberrantly expressed MUC1 and MUC13 might be involved in intestinal barrier dysfunction upon inflammation by affecting junctional and cell polarity proteins, indicating their potential as therapeutic targets in IBD.
    MeSH term(s) Actins/metabolism ; Animals ; CD4-Positive T-Lymphocytes/transplantation ; Cell Adhesion Molecules/genetics ; Colitis/chemically induced ; Colitis/immunology ; Colitis/physiopathology ; Colitis, Ulcerative/genetics ; Colitis, Ulcerative/metabolism ; Colitis, Ulcerative/physiopathology ; Crohn Disease/genetics ; Crohn Disease/metabolism ; Crohn Disease/physiopathology ; Cytokines/metabolism ; Dextran Sulfate ; Dextrans/pharmacokinetics ; Disease Models, Animal ; Female ; Fluorescein-5-isothiocyanate/analogs & derivatives ; Fluorescein-5-isothiocyanate/pharmacokinetics ; Humans ; Interleukin-10/metabolism ; Interleukin-1beta/metabolism ; Interleukin-6/metabolism ; Intestinal Mucosa/physiopathology ; Male ; Mice, Inbred BALB C ; Mice, SCID ; Mucins/genetics ; Mucins/metabolism ; Myosin-Light-Chain Kinase/genetics ; Permeability ; Peroxidase/metabolism ; Tight Junction Proteins/genetics ; Tumor Necrosis Factor-alpha/metabolism
    Chemical Substances Actins ; Cell Adhesion Molecules ; Cytokines ; Dextrans ; IL10 protein, mouse ; IL1B protein, mouse ; Interleukin-1beta ; Interleukin-6 ; MYLK protein, mouse ; Mucins ; Tight Junction Proteins ; Tumor Necrosis Factor-alpha ; fluorescein isothiocyanate dextran ; interleukin-6, mouse ; Interleukin-10 (130068-27-8) ; Dextran Sulfate (9042-14-2) ; Peroxidase (EC 1.11.1.7) ; Myosin-Light-Chain Kinase (EC 2.7.11.18) ; Fluorescein-5-isothiocyanate (I223NX31W9)
    Language English
    Publishing date 2020-01-30
    Publishing country England
    Document type Journal Article
    ZDB-ID 2390120-2
    ISSN 1876-4479 ; 1873-9946
    ISSN (online) 1876-4479
    ISSN 1873-9946
    DOI 10.1093/ecco-jcc/jjaa015
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Regulation of intestinal permeability: The role of proteases.

    Van Spaendonk, Hanne / Ceuleers, Hannah / Witters, Leonie / Patteet, Eveline / Joossens, Jurgen / Augustyns, Koen / Lambeir, Anne-Marie / De Meester, Ingrid / De Man, Joris G / De Winter, Benedicte Y

    World journal of gastroenterology

    2017  Volume 23, Issue 12, Page(s) 2106–2123

    Abstract: The gastrointestinal barrier is - with approximately 400 ... ...

    Abstract The gastrointestinal barrier is - with approximately 400 m
    Language English
    Publishing date 2017-03-28
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 2185929-2
    ISSN 2219-2840 ; 1007-9327
    ISSN (online) 2219-2840
    ISSN 1007-9327
    DOI 10.3748/wjg.v23.i12.2106
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  4. Article ; Online: NecroX-7 reduces necrotic core formation in atherosclerotic plaques of Apoe knockout mice.

    Grootaert, Mandy O J / Schrijvers, Dorien M / Van Spaendonk, Hanne / Breynaert, Annelies / Hermans, Nina / Van Hoof, Viviane O / Takahashi, Nozomi / Vandenabeele, Peter / Kim, Soon Ha / De Meyer, Guido R Y / Martinet, Wim

    Atherosclerosis

    2016  Volume 252, Page(s) 166–174

    Abstract: Background and aims: A large necrotic core is a key feature of atherosclerotic plaque instability. Necrotic cellular debris accumulates in the lipid-rich core and promotes inflammation, destabilization and ultimately rupture of the plaque. Although the ... ...

    Abstract Background and aims: A large necrotic core is a key feature of atherosclerotic plaque instability. Necrotic cellular debris accumulates in the lipid-rich core and promotes inflammation, destabilization and ultimately rupture of the plaque. Although the role of necrosis in atherosclerosis is rather clear-cut, not many strategies have been performed up till now to specifically target plaque necrosis. In the present study, we tested the plaque stabilizing potential of NecroX-7, a novel compound with antioxidative and anti-necrotic properties.
    Methods: Male apolipoprotein E (Apoe) knockout mice were treated with NecroX-7 (30 mg/kg) or vehicle, 3 times per week, via intraperitoneal injections for 16 weeks. Meanwhile, mice were fed a western-type diet to induce plaque formation.
    Results: NecroX-7 reduced total plaque burden in the thoracic aorta as compared to vehicle-treated mice, without affecting total plasma cholesterol. Plaques in the aortic root of NecroX-7-treated mice showed a significant decrease in necrotic core area, 8-oxodG, iNOS and MMP13 expression, while collagen content and minimum fibrous cap thickness were increased. Moreover, NecroX-7 treatment reduced the expression of multiple inflammation markers such as TNFα, IL1β, iNOS, HMGB1 and RAGE in a NF-κB-dependent manner. In vitro, NecroX-7 prevented tert-butyl hydroperoxide (tBHP)-induced mitochondrial ROS formation, necrosis, iNOS expression and HMGB1 release in primary macrophages.
    Conclusions: NecroX-7 improves features of plaque stability in Apoe knockout mice by reducing necrotic core formation, oxidative stress and inflammation, and by increasing collagen deposition and fibrous cap thickness. Therefore, NecroX-7 could be a promising pleiotropic drug for the treatment of atherosclerosis.
    MeSH term(s) Animals ; Atherosclerosis/drug therapy ; Atherosclerosis/metabolism ; Bone Marrow Cells/cytology ; Cholesterol, LDL/metabolism ; Collagen/metabolism ; HMGB1 Protein/metabolism ; Inflammation ; Lipid Peroxidation ; Macrophages/cytology ; Macrophages/metabolism ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout, ApoE ; Necrosis ; Organic Chemicals/pharmacology ; Oxidative Stress ; Plaque, Atherosclerotic/drug therapy ; Plaque, Atherosclerotic/metabolism
    Chemical Substances Cholesterol, LDL ; HMGB1 Protein ; HMGB1 protein, mouse ; Organic Chemicals ; necrox-7 ; Collagen (9007-34-5)
    Language English
    Publishing date 2016
    Publishing country Ireland
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 80061-2
    ISSN 1879-1484 ; 0021-9150
    ISSN (online) 1879-1484
    ISSN 0021-9150
    DOI 10.1016/j.atherosclerosis.2016.06.045
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    Zs.A 226: Show issues Location:
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  5. Article ; Online: Visceral hypersensitivity in inflammatory bowel diseases and irritable bowel syndrome: The role of proteases.

    Ceuleers, Hannah / Van Spaendonk, Hanne / Hanning, Nikita / Heirbaut, Jelena / Lambeir, Anne-Marie / Joossens, Jurgen / Augustyns, Koen / De Man, Joris G / De Meester, Ingrid / De Winter, Benedicte Y

    World journal of gastroenterology

    2016  Volume 22, Issue 47, Page(s) 10275–10286

    Abstract: Proteases, enzymes catalyzing the hydrolysis of peptide bonds, are present at high concentrations in the gastrointestinal tract. Besides their well-known role in the digestive process, they also function as signaling molecules through the activation of ... ...

    Abstract Proteases, enzymes catalyzing the hydrolysis of peptide bonds, are present at high concentrations in the gastrointestinal tract. Besides their well-known role in the digestive process, they also function as signaling molecules through the activation of protease-activated receptors (PARs). Based on their chemical mechanism for catalysis, proteases can be classified into several classes: serine, cysteine, aspartic, metallo- and threonine proteases represent the mammalian protease families. In particular, the class of serine proteases will play a significant role in this review. In the last decades, proteases have been suggested to play a key role in the pathogenesis of visceral hypersensitivity, which is a major factor contributing to abdominal pain in patients with inflammatory bowel diseases and/or irritable bowel syndrome. So far, only a few preclinical animal studies have investigated the effect of protease inhibitors specifically on visceral sensitivity while their effect on inflammation is described in more detail. In our accompanying review we describe their effect on gastrointestinal permeability. On account of their promising results in the field of visceral hypersensitivity, further research is warranted. The aim of this review is to give an overview on the concept of visceral hypersensitivity as well as on the physiological and pathophysiological functions of proteases herein.
    MeSH term(s) Abdominal Pain/drug therapy ; Abdominal Pain/enzymology ; Abdominal Pain/etiology ; Abdominal Pain/physiopathology ; Animals ; Humans ; Hyperalgesia/drug therapy ; Hyperalgesia/enzymology ; Hyperalgesia/etiology ; Hyperalgesia/physiopathology ; Inflammatory Bowel Diseases/complications ; Inflammatory Bowel Diseases/drug therapy ; Inflammatory Bowel Diseases/enzymology ; Inflammatory Bowel Diseases/physiopathology ; Intestinal Absorption ; Intestines/enzymology ; Intestines/innervation ; Irritable Bowel Syndrome/complications ; Irritable Bowel Syndrome/drug therapy ; Irritable Bowel Syndrome/enzymology ; Irritable Bowel Syndrome/physiopathology ; Peptide Hydrolases/metabolism ; Permeability ; Protease Inhibitors/therapeutic use ; Receptors, Proteinase-Activated/metabolism ; Signal Transduction
    Chemical Substances Protease Inhibitors ; Receptors, Proteinase-Activated ; Peptide Hydrolases (EC 3.4.-)
    Language English
    Publishing date 2016-12-07
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 2185929-2
    ISSN 2219-2840 ; 1007-9327
    ISSN (online) 2219-2840
    ISSN 1007-9327
    DOI 10.3748/wjg.v22.i47.10275
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