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Epithelial Tight Junctions in Intestinal Inflammation

Published on May 1, 2009in Annals of the New York Academy of Sciences4.29
· DOI :10.1111/j.1749-6632.2009.04062.x
Joerg D. Schulzke12
Estimated H-index: 12
,
Svenja Ploeger1
Estimated H-index: 1
+ 7 AuthorsMichael Fromm63
Estimated H-index: 63
(Charité)
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Abstract
The epithelium in inflamed intestinal segments of patients with Crohn's disease is characterized by a reduction of tight junction strands, strand breaks, and alterations of tight junction protein content and composition. In ulcerative colitis, epithelial leaks appear early due to micro-erosions resulting from upregulated epithelial apoptosis and in addition to a prominent increase of claudin-2. Th1-cytokine effects by interferon-γ in combination with TNFα are important for epithelial damage in Crohn's disease, while interleukin-13 (IL-13) is the key effector cytokine in ulcerative colitis stimulating apoptosis and upregulation of claudin-2 expression. Focal lesions caused by apoptotic epithelial cells contribute to barrier disturbance in IBD by their own conductivity and by confluence toward apoptotic foci or erosions. Another type of intestinal barrier defect can arise from α-hemolysin harboring E. coli strains among the physiological flora, which can gain pathologic relevance in combination with proinflammatory cytokines under inflammatory conditions. On the other hand, intestinal barrier impairment can also result from transcellular antigen translocation via an initial endocytotic uptake into early endosomes, and this is intensified by proinflammatory cytokines as interferon-γ and may thus play a relevant role in the onset of IBD. Taken together, barrier defects contribute to diarrhea by a leak flux mechanism (e.g., in IBD) and can cause mucosal inflammation by luminal antigen uptake. Immune regulation of epithelial functions by cytokines may cause barrier dysfunction not only by tight junction impairments but also by apoptotic leaks, transcytotic mechanisms, and mucosal gross lesions.
  • References (30)
  • Citations (218)
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References30
Newest
Published on Jun 1, 2008in Journal of Nutrition4.42
Maren Amasheh15
Estimated H-index: 15
(Charité),
S. Schlichter1
Estimated H-index: 1
(Charité)
+ 4 AuthorsJörg D. Schulzke15
Estimated H-index: 15
(Charité)
Quercetin is the most abundant flavonoid and is assumed to have positive effects on the gastrointestinal mucosa after dietary intake. The aim of the study was to analyze the influence of quercetin on intestinal barrier function using the human colonic epithelial cell line Caco-2. Transepithelial resistance (R t ), tracer fluxes of [ 3 H]-mannitol, 22 Na + , and 36 Cl - as well as electrogenic ion transport were determined in Ussing chambers. Expression of tight junction (TJ) proteins and mRNA wa...
Published on Feb 13, 2008in Gut17.94
Michael Schumann26
Estimated H-index: 26
,
Jan F. Richter20
Estimated H-index: 20
+ 7 AuthorsJörg-Dieter Schulzke55
Estimated H-index: 55
Background and aims: The α 2 -gliadin-33mer has been shown to be important in the pathogenesis of coeliac disease. We aimed to study mechanisms of its epithelial translocation and processing in respect to transcytotic and paracellular pathways. Methods: Transepithelial passage of a fluorescence-labelled α 2 -gliadin-33mer was studied in Caco-2 cells by using reverse-phase high-performance liquid chromatography, mass spectrometry, confocal laser scanning microscopy (LSM) and fluorescence activate...
Published on Oct 1, 2007in Cellular Microbiology4.29
Hanno Troeger12
Estimated H-index: 12
(Charité),
Jan F. Richter20
Estimated H-index: 20
(Charité)
+ 7 AuthorsJörg-Dieter Schulzke55
Estimated H-index: 55
(Charité)
Extraintestinal pathogenic Escherichia coli (ExPEC) are usually harmless colonizer of the intestinal microflora. However, they are capable to translocate and cause life-threatening disease. Translocation of ExPEC isolates was quantified in colonic monolayers. Transepithelial resistance (R(t)) was monitored and local changes in conductivity analysed with conductance scanning. Confocal microscopy visualized the translocation route. Corroboratory experiments were performed on native rat colon. One ...
Published on Jan 1, 2007in Gut17.94
Sebastian Zeissig29
Estimated H-index: 29
,
Nataly Bürgel4
Estimated H-index: 4
+ 7 AuthorsJoerg D. Schulzke12
Estimated H-index: 12
Background: Epithelial barrier function is impaired in Crohn’s disease. Aim: To define the underlying cellular mechanisms with special attention to tight junctions. Methods: Biopsy specimens from the sigmoid colon of patients with mild to moderately active or inactive Crohn’s disease were studied in Ussing chambers, and barrier function was determined by impedance analysis and conductance scanning. Tight junction structure was analysed by freeze fracture electron microscopy, and tight junction p...
Published on Jan 1, 2006in PLOS Pathogens6.46
Mickey Pentecost2
Estimated H-index: 2
(Stanford University),
Glen Otto6
Estimated H-index: 6
(Stanford University)
+ 1 AuthorsManuel R. Amieva32
Estimated H-index: 32
(Stanford University)
Listeria monocytogenes causes invasive disease by crossing the intestinal epithelial barrier. This process depends on the interaction between the bacterial surface protein Internalin A and the host protein E-cadherin, located below the epithelial tight junctions at the lateral cell-to-cell contacts. We used polarized MDCK cells as a model epithelium to determine how L. monocytogenes breaches the tight junctions to gain access to this basolateral receptor protein. We determined that L. monocytoge...
Published on Aug 1, 2005in Gastroenterology19.23
Frank Heller14
Estimated H-index: 14
(Charité),
Peter Florian10
Estimated H-index: 10
(Charité)
+ 11 AuthorsMichael Fromm63
Estimated H-index: 63
(Charité)
Background & Aims: Ulcerative colitis (UC) is characterized by a Th2 immune response with inflammation and epithelial barrier dysfunction. So far, Th2 cytokines have not been shown to directly influence epithelial barrier function. Methods: Lamina propria mononuclear cells (LPMCs) were stimulated and interleukin (IL)-13 was measured by enzyme-linked immunosorbent assay. Functional IL-13 and IL-4 effects were studied on HT-29/B6 colonic epithelial cells in Ussing chambers and by conductance scann...
Published on Mar 15, 2005in Drug Discovery Today6.88
James M. Mullin29
Estimated H-index: 29
(Lankenau Institute for Medical Research),
Nicole Agostino1
Estimated H-index: 1
(Lankenau Institute for Medical Research)
+ 1 AuthorsJames J. Thornton7
Estimated H-index: 7
There is a spectrum of distinct disease states that have in common their effect of breaking down epithelial and/or endothelial barrier function. Fluid compartmentalization goes awry, with profound implications for epithelial and stromal homeostasis, fluid and/or electrolyte balance, generation of inflammatory states, and even tumor microenvironment. Specific effects on the tight junction are found to be integral to bacterial invasion and tumor progression.
Published on Dec 1, 2004in Gut17.94
Johan D. Söderholm45
Estimated H-index: 45
(Linköping University),
C Streutker1
Estimated H-index: 1
+ 6 AuthorsMary H. Perdue56
Estimated H-index: 56
Background and aims: The exact nature of the epithelial barrier defect in Crohn's disease remains to be elucidated. Previously we showed increased permeability to proteins in ileal Crohn's disease. Our aims were to study if this barrier defect (a) involves endocytotic uptake of antigens and (b) is related to low grade inflammation not detectable by histology. Methods: Macroscopically normal segments of distal ileum of Crohn's disease patients (n = 10) were subgrouped into non-inflamed (histologi...
Published on Sep 1, 2004in Gut17.94
Sebastian Zeissig29
Estimated H-index: 29
,
Christian Bojarski20
Estimated H-index: 20
+ 4 AuthorsJörg-Dieter Schulzke55
Estimated H-index: 55
Background and aims: Barrier dysfunction is an important feature contributing to inflammation and diarrhoea in Crohn’s disease (CD). Recently, tumour necrosis factor α (TNF-α) antibodies were recognised as effective in steroid refractory CD. The aim of this study was to characterise the effects of this therapy on the epithelial barrier. Patients and methods: Forceps biopsies were obtained from the sigmoid colon before and 14 days after TNF-α antibody therapy in 11 patients treated for chronic ac...
Published on Aug 1, 2004in American Journal of Pathology3.76
Sabine Kersting3
Estimated H-index: 3
(WWU: University of Münster),
Matthias Bruewer25
Estimated H-index: 25
(WWU: University of Münster)
+ 8 AuthorsHassan Y. Naim35
Estimated H-index: 35
Intestinal antigen uptake is enhanced in inflammatory bowel disease. We analyzed transcellular transport routes of antigens in different compartments of normal enterocytes and atypical intestinal epithelial cells called “rapid antigen uptake into the cytosol enterocytes” (RACE cells). These cells constitute a recently described population of enterocyte-derived cells, which are increased in inflammatory bowel disease. Mucosa of freshly resected specimens wereincubated with the antigens ovalbumin ...
Cited By218
Newest
Published on Jan 9, 2019in Nature Communications11.88
Rajbir Singh2
Estimated H-index: 2
(University of Louisville),
Sandeep Chandrashekharappa1
Estimated H-index: 1
+ 18 AuthorsMatam Vijay-Kumar31
Estimated H-index: 31
(UT: University of Toledo)
The importance of gut microbiota in human health and pathophysiology is undisputable. Despite the abundance of metagenomics data, the functional dynamics of gut microbiota in human health and disease remain elusive. Urolithin A (UroA), a major microbial metabolite derived from polyphenolics of berries and pomegranate fruits displays anti-inflammatory, anti-oxidative, and anti-ageing activities. Here, we show that UroA and its potent synthetic analogue (UAS03) significantly enhance gut barrier fu...
Published on Dec 1, 2019in Scientific Reports4.01
Ernest T. Chivero7
Estimated H-index: 7
(UNMC: University of Nebraska Medical Center),
Rizwan Ahmad9
Estimated H-index: 9
(UNMC: University of Nebraska Medical Center)
+ 9 AuthorsPunita Dhawan6
Estimated H-index: 6
(UNMC: University of Nebraska Medical Center)
Cocaine use disorder (CUD), a major health crisis, has traditionally been considered a complication of the CNS; however, it is also closely associated with malnourishment and deteriorating gut health. In light of emerging studies on the potential role of gut microbiota in neurological disorders, we sought to understand the causal association between CUD and gut dysbiosis. Using a comprehensive approach, we confirmed that cocaine administration in mice resulted in alterations of the gut microbiot...
Published on Sep 18, 2019in Mucosal Immunology7.35
Yuli Lin6
Estimated H-index: 6
(Fudan University),
Bingji Li5
Estimated H-index: 5
(Fudan University)
+ 7 AuthorsRui He20
Estimated H-index: 20
(Fudan University)
Enhanced gut permeability due to dysregulated epithelial tight junction is often associated with inflammatory bowel diseases (IBD), which have a greater risk for developing colorectal cancer. STAT6 activation was detected in inflamed colonic epithelium of active IBD patients, suggesting a role of epithelial STAT6 in colitis development. Here, we demonstrated that non-hematopoietic STAT6, but not hematopoietic STAT6, triggered DSS-induced colitis and subsequent tumorigenesis. This could be due to...
Published on Sep 13, 2019in Frontiers in Immunology4.72
Quan Yang3
Estimated H-index: 3
(Guangzhou Medical University),
Jiale Qu3
Estimated H-index: 3
(Guangzhou Medical University)
+ 8 AuthorsYanwei Qi2
Estimated H-index: 2
(Guangzhou Medical University)
CD4+ T follicular helper (Tfh) cells, a new subset of immune cells, have been demonstrated to be involved in granulomatous responses to Schistosoma japonicum (S. japonicum) infection. However, their role and the detailed mechanisms of Tfh cell aggregation remain to be described. In this study, we provide evidence that S. japonicum infection enhances the accumulation of Tfh cells in the spleen, lymph nodes, and peripheral blood of C57BL/6 mice. Infection-induced Tfh cells have a more potent facil...
Published on 2019in Molecules3.06
Sihao Gu , Ling Li1
Estimated H-index: 1
+ 2 AuthorsTong Zhang9
Estimated H-index: 9
Atractylodes macrocephala Koidz. has been used as an invigorating spleen drug for eliminating dampness and phlegm in China. According to recent researches, different processing methods may affect the drug efficacy, so we collected A. macrocephala from the Zhejiang Province, produced with different processing methods, crude A. macrocephala (CA) and bran-processed A. macrocephala (BA), then analyzed its essential oils (EOs) by GC/MS. The results showed 34 components representing 98.44% of the tota...
Hajara Aslam1
Estimated H-index: 1
(Deakin University),
Anu Ruusunen13
Estimated H-index: 13
(University of Eastern Finland)
+ 4 AuthorsFelice N. Jacka44
Estimated H-index: 44
(Deakin University)
AbstractBeyond being a source of key nutrients, bovine milk influences physiological functions by synthesising bioactive peptides during the process of digestion. Some of the claimed negative health outcomes associated with milk consumption, such as cardiovascular diseases and type 1 diabetes may be attributed to an opioid peptide, beta-casomorphin-7 (BCM-7), derived from A1 beta-casein. BCM-7 exerts its function by binding to the μ-opioid receptors in the body. It is hypothesised that activatio...
Published on Mar 10, 2018in European Journal of Nutrition4.45
Yvonne Hagenlocher5
Estimated H-index: 5
(University of Hohenheim),
Sonja Gommeringer1
Estimated H-index: 1
(University of Hohenheim)
+ 4 AuthorsAxel Lorentz26
Estimated H-index: 26
(University of Hohenheim)
Purpose Inflammatory bowel disease (IBD) shows increasing prevalence over the last years. We propose that anti-inflammatory plant substances could be used as additional or alternative agents with good compliance in prevention and/or therapy of IBD and its complication intestinal fibrosis. We could recently show that the citrus flavonoid nobiletin acts anti-inflammatory on activation of intestinal mast cells. Here, we analysed the effects of nobiletin on inflammation and fibrosis in IL-10−/− coli...
Published on Mar 18, 2019in Frontiers in Microbiology4.26
Svetlana Sokovic Bajic (University of Belgrade), Jelena Djokic7
Estimated H-index: 7
(University of Belgrade)
+ 4 AuthorsMaja Tolinacki9
Estimated H-index: 9
(University of Belgrade)
Probiotic bacteria are recognized for their health-promoting properties, including maintenance of gut epithelial integrity and host immune system homeostasis. Taking into account the beneficial health-promoting effects of GABA, the presence of the gadB gene, encoding glutamate decarboxylase that converts L-glutamate to GABA, was analyzed in Lactic Acid Bacteria (LAB) natural isolates from Zlatar cheese. The results revealed that 52% of tested Lactobacillus spp. and 8% of Lactococcus spp. isolate...
Published on Feb 1, 2019in Journal of Dairy Science3.08
Zhengyuan Zhai (CAU: China Agricultural University), Jiaojiao Wang (CAU: China Agricultural University)+ 1 AuthorsSheng Yin (BTBU: Beijing Technology and Business University)
ABSTRACT Yogurt is a source of bioactive compounds and probiotic microorganisms that modify immunity and metabolism to benefit human health beyond nutrition. In this study, we examined the capacity of yogurt to prevent epithelial barrier disruption in vitro . Different preparations of yogurt were added apically to Caco-2 monolayers before IL-1β exposure. Dulbecco's modified Eagle medium containing 25% (vol/vol) low-fat yogurt prevented cytokine-induced transepithelial resistance reduction and in...
Published on Feb 1, 2019in Nature Reviews Gastroenterology & Hepatology23.57
Eric L. Campbell19
Estimated H-index: 19
('QUB': Queen's University Belfast),
Sean P. Colgan78
Estimated H-index: 78
(University of Colorado Denver)
Redox signalling in the gastrointestinal mucosa is held in an intricate balance. Potent microbicidal mechanisms can be used by infiltrating immune cells, such as neutrophils, to protect compromised mucosae from microbial infection through the generation of reactive oxygen species. Unchecked, collateral damage to the surrounding tissue from neutrophil-derived reactive oxygen species can be detrimental; thus, maintenance and restitution of a breached intestinal mucosal barrier are paramount to hos...
View next paperChanges in expression and distribution of claudin-2, -5 and -8 lead to discontinuous tight junctions and barrier dysfunction in active Crohn's disease