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DFG Research Unit FOR 721/2 Molecular Structure and Function of the Tight Junction |
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Project 2 |
Jörg-Dieter Schulzke, Prof. Dr.
,
Division of
Nutritional Medicine, Dept. of Gastroenterology, Infectiology and Rheumatology,
Campus Benjamin Franklin, Charité, Freie Universität und
Humboldt-Universität, Berlin
Martin Zeitz, Prof. Dr.
,
Dept. of
Gastroenterology, Infectiology and Rheumatology,
Campus Benjamin Franklin, Charité, Freie Universität und
Humboldt-Universität, Berlin
Tight junction proteins in inflammatory bowel diseases
In microscopic colitis and in ulcerative colitis before and after therapy, mechanisms of epithelial barrier dysfunction are analyzed using impedance spectroscopy, scanning conductance, confocal microscopy, Western blotting, and quantitative RT-PCR analysis. During this, the expression of the tight junction molecules ZO1, occludin, tricellulin, and supposedly important claudins are characterized. In addition, apoptosic rates and epithelial lesions are assayed.
Furthermore, mechanisms of the inflammatory regulation of epithelial tight junctions and their constituent molecules are studied in HT-29/B6 colon cells. Parameter are half life, subcellular distribution, mRNA expression, translational efficiency as effectd by by miRNAs, promoter activity, and intracellular signaling pathways.
Granted by project 2
Dr. Nina A. Hering
Dipl.-Biol. Lena J. John (doctoral
Coworkers
Dr. Maren Amasheh
Dipl. Biol. Svenja
Ploeger
2012
Amasheh M, Luettig J, Amasheh S, Zeitz M, Fromm M, Schulzke JD (2012) Effects of quercetin on the colonic cell culture model HT-29/B6 and rat intestine in vitro. Ann. N.Y. Acad. Sci. 1258: 100-107 (IF 3.2) [PubMed] [WebPage] [PDF] (Original paper) TP2+TP1
Barmeyer C, Erko I, Fromm A, Bojarski C, Allers C, Moos V, Zeitz M, Fromm M, Schulzke JD (2012) Ion transport and barrier function are disturbed in microscopic colitis. Ann. N.Y. Acad. Sci. 1258: 143-148 (IF 3.2) [PubMed] [WebPage] [PDF] (Original paper) TP2+TP1
Batra A, Heimesaat MM, Bereswill S, Fischer A, Glauben R, Kunkel D, Scheffold A, Erben U, Kühl A, Loddenkemper C, Lehr HA, Schumann M, Schulzke JD, Zeitz M, Siegmund B (2012) Mesenteric fat – control site for bacterial translocation in colitis? Mucosal Immunol. 5(5): 580-591 (IF 7.0) [PubMed] [HTML] [PDF] TP2
Krug SM, Günzel D, Conrad MP, Rosenthal R, Fromm A, Amasheh S, Schulzke JD, Fromm M (2012) Claudin-17 forms tight junction channels with distinct anion selectivity. Cell. Mol. Life Sci. 69(16): 2765-2778 (IF 6.6) [PubMed] [WebPage] [PDF] [Supplement] TP1+TP7+TP2
Ménard S, Lebreton C, Schumann M, Matysiak-Budnik T, Dugave C, Bouhnik Y, Malamut G, Cellier C, Allez M, Crenn P, Schulzke JD, Cerf-Bensussan N, Heyman M (2012) Paracellular versus transcellular intestinal permeability to gliadin peptides in active celiac disease. Am. J. Pathol. 180(2): 608-615 (IF 4.9) [PubMed] [HTML] [PDF] TP2
Rosenthal R*, Günzel D* (*shared first authorship), Finger C, Krug SM, Richter JF, Schulzke JD, Fromm M, Amasheh S (2012) The effect of chitosan on transcellular and paracellular mechanisms in the intestinal epithelial barrier. Biomaterials 33(9): 2791-2800 (IF 7.9) [PubMed] [HTML] [PDF] [Supplement] TP1+TP7+TP2+TPZ
Schumann M, Günzel D, Buergel N, Richter JF, Troeger H, May C, Fromm A, Sorgenfrei D, Daum S, Bojarski C, Heyman M, Zeitz M, Fromm M, Schulzke JD 2012) Cell polarity-determining proteins Par-3 and PP-1 are involved in epithelial tight junction defects in celiac disease. Gut 61(2): 220-228 (IF 10.1) [PubMed] [HTML] [PDF] [Supplements] TP2+TP7+TP1
Schumann M, Kamel S, Pahlitzsch ML, Lebenheim L, May C, Krauss M, Hummel M, Daum S, Fromm M, Schulzke JD (2012) Defective tight junctions in refractory celiac disease. Ann. N.Y. Acad. Sci. 1258: 43-51 (IF 3.2) [PubMed] [WebPage] [PDF] (Original paper) TP2+TP1
Reviews
Hering NA, Fromm M, Schulzke JD (2012) Determinants of colonic barrier function in inflammatory bowel disease and potential therapeutics. J. Physiol. 590(5): 1035-1044 (IF 5.1) [PubMed] [HTML] [PDF] (Review) TP2+TP1
Plöger S, Stumpff F, Penner GB, Schulzke JD, Gäbel G, Martens H, Shen Z, Günzel D, Aschenbach JR (2012) Microbial butyrate and its role for barrier function in the gastrointestinal tract. Ann. N.Y. Acad. Sci. 1258: 52-59 (IF 3.2) [PubMed] [WebPage] [PDF] (Review) TP2+TP7
Schulzke JD, Günzel D, John LJ, Fromm M (2012) Perspectives in tight junction research. Ann. N.Y. Acad. Sci. (IF 3.2) [16.02.12 Accepted] (Review) TP2+TP7+TP1
Editions
Fromm M, Schulzke JD, Volume Editors (2012)
Fromm M, Schulzke JD, Volume Editors (2012) Barriers and channels formed by tight junction proteins II. Ann. N.Y. Acad. Sci. vol. 1258: ###-###, 24 papers [In press]
2011
Bücker R, Krug SM, Rosenthal R, Günzel D, Fromm A, Zeitz M, Chakraborty T, Fromm M, Epple HJ, Schulzke JD (2011) Aerolysin from Aeromonas hydrophila perturbs tight junction integrity and cell lesion repair in intestinal epithelial HT-29/B6 cells. J. Infect. Dis. 204 (8): 1283-1292 [PubMed] [HTML] [PDF] TP2+TP1+TP7+TPZ
Hering NA*, Andres S* (*shared first authorship), Fromm A, van Tol EA, Amasheh M, Mankertz J, Fromm M, Schulzke JD (2011) Transforming growth factor b, a whey protein component, strengthens the intestinal barrier by upregulating claudin-4 in HT-29/B6 cells. J. Nutr. 141(5): 783-789 [PubMed] [HTML] [PDF] TP2+TP1
Hering NA, Richter JF, Krug SM, Günzel D, Fromm A, Bohn E, Rosenthal R, Bücker R, Fromm M, Troeger H, Schulzke JD (2011) Yersinia enterocolitica induces epithelial barrier dysfunction through regional tight junction changes in colonic HT-29/B6 cell monolayers. Lab. Invest. 91: 310-324 [PubMed] [HTML] [PDF] [Supplement DOC]
John LJ, Fromm M, Schulzke JD (2011) Epithelial barriers in intestinal inflammation. Antioxid. Redox Signal. 15(5): 1255-1270 (IF 8.2) (Review) [PubMed] [HTML] [PDF for printing] [PDF with links] TP2+TP1
Nielsen HL, Nielsen H, Ejlertsen T, Engberg J, Günzel D, Zeitz M, Hering NA, Fromm M, Schulzke JD, Bücker R (2011) Oral and fecal Campylobacter concisus strains perturb barrier function by apoptosis induction in HT-29/B6 intestinal epithelial cells. Plos One 6(8): e23858 (print pages 1-8) [PubMed] [HTML] [PDF] TP2+TP7+TP1
Schulzke JD*, Andres S*, Amasheh M* (*shared first authorship), Fromm A, Günzel D (2011) Anti-diarrheal mechanism of the traditional remedy Uzara via reduction of active chloride secretion. PLoS One 6(3): e18107 (print 1-9) [PubMed] [HTML] [PDF]
2010
Amasheh M, Fromm A, Krug SM, Amasheh S, Andres S, Zeitz M, Fromm M, Schulzke JD (2010) TNFa-induced and berberine-antagonized tight junction barrier impairment via tyrosine kinase, pAkt, and NFkB signaling. J. Cell Sci. 123(23): 4145-4155 [PubMed] [HTML] [PDF] [Supplements]
Bücker R, Schumann M, Amasheh S, Schulzke JD (2010) Claudins in intestinal function and disease. Curr. Top. Membr. 65: 195-227 [Directory] [HTML] [PDF] (Review / book chapter)
Epple HJ, Allers K, Tröger H, Kühl
A, Erben U, Fromm M, Zeitz M, Loddenkemper C*, Schulzke JD*,
Schneider T* (*shared last authorship) (2010) Acute HIV infection induces
mucosal infiltration with CD4+ and CD8+ T cells, epithelial apoptosis, and a
mucosal barrier defect. Gastroenterology
139(4): 1289-1300 [PubMed]
[HTML]
[PDF]
[Supplement
PDF]
Hillenbrand B, Günzel D, Richter JF, Höhne, Schreier E, Schulzke JD, Mankertz J (2010) Norovirus non-structural protein p20 leads to impaired restitution of epithelial defects by inhibition of actin cytoskeleton remodelling. Scand. J. Gastroent. 45(11):1307-1319 [PubMed] [HTML] [PDF]
Milatz S, Krug SM, Rosenthal R, Günzel D, Müller D, Schulzke JD, Amasheh S*, Fromm M* (*shared last authorship) (2010) Claudin-3 acts as a sealing component of the tight junction for ions of either charge and uncharged solutes. Biochim. Biophys. Acta Biomembr. 1798: 2048-2057 [PubMed] [HTML] [PDF]
Rosenthal R, Milatz S, Krug SM,
Oelrich B, Schulzke JD, Amasheh S, Günzel D, Fromm M (2010) Claudin-2,
a component of the tight junction, forms a paracellular water channel.
J. Cell Sci. 123(11): 1913-1921 [PubMed]
[HTML] [PDF]
[Supplement]
Doctoral theses
Ploeger S (2011) [The
short-chain fatty acid, butyrate, stabilizes the intestinal epithelial barrier
function by HNF-4alpha-dependent down-regulation of claudin-2 expression].
Doctoral thesis, Biology, FU
Berlin, 17.06.11: Dr. rer. nat., Magna cum laude
Hering NA (2010) [The
epithelial barrier as a target structure for pathogenic and probiotic
bacteria: effector mechanisms of Y. enterocolitica and E. coli
Nissle]. Doctoral Thesis, Biology,
Freie Universität Berlin. 14.12.10: Dr. rer. nat.,
Magna cum laude
Publications 2007 - 2009 (FOR 721/1)
Amasheh M, Grotjohann I, Amasheh S, Fromm A, Söderholm JD, Zeitz M, Fromm M, Schulzke JD (2009) Regulation of mucosal structure and barrier function in rat colon exposed to tumor necrosis factor alpha and interferon gamma in vitro: A novel model for studying the pathomechanisms of inflammatory bowel disease cytokines. Scand. J. Gastroent. 44: 1226-1235 [PubMed] [HTML] [PDF]
Amasheh S, Dullat S, Fromm M, Schulzke JD, Buhr HJ, Kroesen AJ (2009) Inflamed pouch mucosa possesses altered tight junctions indicating recurrence of inflammatory bowel disease. Int. J. Colorectal Dis. 24(10): 1149-1156 [PubMed] [HTML] [PDF]
Hering NA, Schulzke JD (2009) Therapeutic options to modulate barrier defects in inflammatory bowel disease. Dig. Dis. 27(4): 450-454 [PubMed] [PDF] (Review)
Krug SM, Amasheh S, Richter JF, Milatz S, Günzel D, Westphal JK, Huber O, Schulzke JD, Fromm M (2009) Tricellulin forms a barrier to macromolecules in tricellular tight junctions without affecting ion permeability. Mol. Biol. Cell 20: 3713-3724 [PubMed] [HTML] [PDF] [Supplement text] [Supplement video]
Bücker R*, Troeger H* (shared first authorship), Kleer J, Fromm M, Schulzke JD (2009) Arcobacter butzleri induces barrier dysfunction in intestinal epithelial cells. J. Infect. Dis. 200(5): 756-764 [PubMed] [HTML] [PDF]
Mankertz J*, Amasheh M* (shared first authorship), Krug SM, Fromm A, Amasheh S, Hillenbrand B, Tavalali S, Fromm M, Schulzke JD (2009) TNFalpha up-regulates claudin-2 expression in epithelial HT-29/B6 cells via phosphatidylinositol-3-kinase signaling. Cell Tiss. Res. 336(1): 67-77 [PubMed] [HTML] [PDF]
Troeger H, Loddenkemper C, Schneider T, Schreier E, Epple HJ, Zeitz M, Fromm M, Schulzke JD (2009) Structural and functional changes of the duodenum in human norovirus infection. Gut 58: 1070-1077 [PubMed] [HTML] [PDF]
Amasheh S*, Milatz S* (shared first authorship), Krug SM, Bergs M, Amasheh M, Schulzke JD, Fromm M (2009, Epub 08.11.2008) Na+ absorption defends from paracellular back-leakage by claudin-8 upregulation. Biochem. Biophys. Res. Comm. 378(1): 45-50 [PubMed] [HTML] [PDF]
Amasheh M, Schlichter S, Amasheh S, Mankertz J, Zeitz M, Fromm M, Schulzke JD (2008) Quercetin enhances epithelial barrier function and increases claudin-4 expression in Caco-2 cells. J. Nutr. 138(6): 1067-1073 [PubMed] [HTML] [PDF]
Epple HJ, Schneider T, Troeger H, Kunkel D, Allers K, Moos V, Amasheh M, Loddenkemper C, Fromm M, Zeitz M, Schulzke JD (2009, Epub 04.11.2008) Impairment of the intestinal barrier is evident in untreated but absent in suppressively treated HIV-infected patients. Gut 58: 220-227 [PubMed] [HTML] [PDF]
Kroesen AJ, Dullat S, Schulzke JD, Fromm M, Buhr HJ (2008) Permanently increased mucosal permeability in patients with backwashileitis after ileoanal pouch for ulcerative colitis. Scand. J. Gastroent. 43(6): 704-711 [PubMed] [HTML] [PDF]
Schumann M, Richter JF, Wedell I, Moos V, Zimmermann-Kordmann M, Schneider T, Daum S, Zeitz M, Fromm M, Schulzke JD (2008) Mechanisms of epithelial translocation of the a2-gliadin-33mer in celiac sprue. Gut 57(6): 747-754 [PubMed] [HTML] [PDF]
Mankertz J, Schulzke JD (2007) Altered permeability in inflammatory bowel disease: pathophysiology and clinical implications. Curr. Opin. Gastroenterol. 23(4): 379-383 [PubMed] [HTML/PDF]
Troeger H, Epple HJ, Schneider T, Wahnschaffe U, Ullrich R, Burchard GD, Jelinek T, Zeitz M, Fromm M, Schulzke JD (2007) Effect of chronic Giardia lamblia infection on epithelial transport and barrier function in human duodenum. Gut 56(3): 328-335 [PubMed] [HTML] [PDF] Comment in: Gut 2007 56(3): 316-317
Zeissig S, Bürgel N, Günzel D, Richter JF, Mankertz J, Wahnschaffe U, Kroesen AJ, Zeitz M, Fromm M, Schulzke JD (2007) Changes in expression and distribution of claudin-2, -5 and -8 lead to discontinuous tight junctions and barrier dysfunction in active Crohn's disease. Gut 56(1): 61-72 [PubMed] [HTML] [PDF]
Ann. N.Y. Acad. Sci. 1165 [Contents and Full Papers]
Fromm M, Schulzke JD, Volume Editors (2009) Molecular structure and function of the tight junction. Ann. N.Y. Acad. Sci. 1165, pp 1-346 [Contents and Full Papers] [Cover]
Amasheh M, Andres S, Amasheh S, Fromm M, Schulzke JD (2009) Barrier effects of nutritional factors. Ann. N.Y. Acad. Sci. 1165: 267-273 [PubMed] [HTML] [PDF]
Fromm M, Krug SM, Zeissig S, Richter JF, Rosenthal R, Schulzke JD, Günzel D (2009) High resolution analysis of barrier function. Ann. N.Y. Acad. Sci. 1165: 74-81 [PubMed] [HTML] [PDF]
Schulzke JD, Fromm M (2009) Tight junctions: Molecular structure meets function. Ann. N.Y. Acad. Sci. 1165: 1-6 [PubMed] [HTML] [PDF]
Schulzke JD*, Ploeger S* (shared first authorship), Amasheh M, Fromm A, Zeissig S, Troeger H, Richter JF, Bojarski C, Schumann M, Fromm M (2009) Epithelial tight junctions in intestinal inflammation. Ann. N.Y. Acad. Sci. 1165: 294-300 [PubMed] [HTML] [PDF]
Previous work
Bojarski C, Weiske J, Schöneberg T, Schröder W, Mankertz J, Schulzke JD, Florian P, Fromm M, Tauber R, Huber O (2004) The specific fates of tight junction proteins in apoptotic epithelial cells. J. Cell Sci. 117: 2097-2107.
Bürgel N, Bojarski C, Mankertz J, Zeitz M, Fromm M, Schulzke JD (2002) Mechanisms of diarrhea in collagenous colitis. Gastroenterology 123: 433-443.
Epple HJ, Amasheh S, Mankertz J, Goltz M, Schulzke JD, Fromm M (2000) Early aldosterone effect in distal colon by transcriptional regulation of ENaC subunits. Am. J. Physiol. 278: G718-G724.
Gitter AH, Wullstein F, Fromm M, Schulzke JD (2001) Epithelial barrier defects in ulcerative colitis: characterization and quantification by electrophysiological imaging. Gastroenterology 121: 1320-1328.
Grotjohann I, Fromm M, Schulzke JD (2000) Effect of tumor necrosis factor a on rat rectum in vitro. Ann. N.Y. Acad. Sci. 915: 282-286.
Heller F, Florian P, Bojarski C, Richter J, Christ M, Hillenbrand B, Mankertz J, Gitter AH, Bürgel N, Fromm M, Zeitz M, Fuss I, Strober W, Schulzke JD (2005) Interleukin-13 is the key effector Th2 cytokine in ulcerative colitis that affects epithelial tight junctions, apoptosis, and cell restitution. Gastroenterology 129: 550-564.
Kroesen AJ, Stockmann M, Ransco C, Schulzke JD, Fromm M, Buhr HJ (2002) Impairment of epithelial transport but not of barrier function in idiopathic pouchitis after ulcerative colitis. Gut 50: 821-826.
Mankertz J, Hillenbrand B* (shared first authorship), Tavalali S, Huber O, Fromm M, Schulzke JD (2004) Functional crosstalk between Wnt signaling and Cdx-related transcriptional activation in the regulation of the claudin-2 promoter activity. Biochem. Biophys. Res. Comm. 314: 1001-1007.
Mankertz J, Tavalali S, Schmitz H, Mankertz A, Fromm M, Schulzke JD (2000) Expression from the human occludin promoter is affected by tumor necrosis factor a and interferon gamma. J. Cell Sci. 113: 2085-2090.
Mankertz J, Waller JS, Hillenbrand B, Tavalali S, Florian P, Schöneberg T, Fromm M, Schulzke JD (2002) Gene expression of the tight junction protein occludin includes differential splicing and alternative promoter usage. Biochem. Biophys. Res. Comm. 298: 657-666.
Saitou M, Furuse M, Sasaki H, Schulzke JD, Fromm M, Takano H, Noda T, Tsukita S (2000) Complex phenotype of mice lacking occludin, a component of tight junction strands. Mol. Biol. Cell 11: 4131-4142.
Schmitz H, Barmeyer C, Fromm M, Runkel N, Foss HD, Bentzel CJ, Riecken EO, Schulzke JD (1999a) A decrease in tight junction complexity contributes to the severely impaired epithelial barrier function in ulcerative colitis. Gastroenterology 116: 301-309.
Schmitz H, Fromm M, Bentzel CJ, Scholz P, Bode H, Epple HJ, Riecken EO, Schulzke JD (1999b) Tumor necrosis factor-alpha (TNFalpha) regulates the epithelial barrier in the human intestinal cell line HT-29/B6. J. Cell Sci. 112: 137-146.
Schulzke JD, Fromm M, Gogarten W, Gebhard H, Schröder P, Riecken EO (1993) Epithelial ion transport in the ileal J-pouch after proctocolectomy in the rat. Scand. J. Gastroenterol. 28: 533-539.
Schulzke JD, Fromm M, Hegel U (1986) Epithelial and subepithelial resistance of rat large intestine: Segmental differences, effect of stripping, time course, and action of aldosterone. Pflügers Arch. 407: 632-637.
Schulzke JD, Gitter AH, Mankertz J, Spiegel S, Seidler U, Amasheh S, Saitou M, Tsukita S, Fromm M (2005) Epithelial transport and barrier function in occludin-deficient mice. Biochim. Biophys. Acta - Biomembranes 1669(1): 34-42.
Zeissig S, Bojarski C, Bürgel N, Mankertz J, Zeitz M, Fromm M, Schulzke JD (2004) Downregulation of epithelial apoptosis and barrier repair in active Crohn’s disease by TNFalpha antibody treatment. Gut 53: 1295-1302.