3,983
Views
162
CrossRef citations to date
0
Altmetric
Review

Claudin-2 as a mediator of leaky gut barrier during intestinal inflammation

, , &
Article: e977176 | Received 03 Sep 2014, Accepted 10 Oct 2014, Published online: 25 Feb 2015

References

  • Anderson JM. Molecular structure of tight junctions and their role in epithelial transport. News Physiol Sci 2001; 16:126-30; PMID:11443232
  • Markov AG, Voronkova MA, Volgin GN, Yablonsky PK, Fromm M, Amasheh S. Tight junction proteins contribute to barrier properties in human pleura. Respir Physiol Neurobiol 2011; 175:331-5; PMID:21187167; http://dx.doi.org/10.1016/j.resp.2010.12.012
  • Amasheh S, Meiri N, Gitter AH, Schoneberg T, Mankertz J, Schulzke JD, Fromm M. Claudin-2 expression induces cation-selective channels in tight junctions of epithelial cells. J Cell Sci 2002; 115:4969-76; PMID:12432083; http://dx.doi.org/10.1242/jcs.00165
  • Rosenthal R, Milatz S, Krug SM, Oelrich B, Schulzke JD, Amasheh S, Gunzel D, Fromm M. Claudin-2, a component of the tight junction, forms a paracellular water channel. J Cell Sci 2010; 123:1913-21; PMID:20460438; http://dx.doi.org/10.1242/jcs.060665
  • Furuse M, Fujita K, Hiiragi T, Fujimoto K, Tsukita S. Claudin-1 and -2: novel integral membrane proteins localizing at tight junctions with no sequence similarity to occludin. J Cell Biol 1998; 141:1539-50; PMID:9647647; http://dx.doi.org/10.1083/jcb.141.7.1539
  • Itoh M, Furuse M, Morita K, Kubota K, Saitou M, Tsukita S. Direct binding of three tight junction-associated MAGUKs, ZO-1, ZO-2, and ZO-3, with the COOH termini of claudins. J Cell Biol 1999; 147:1351-63; PMID:10601346; http://dx.doi.org/10.1083/jcb.147.6.1351
  • Stiffler MA, Chen JR, Grantcharova VP, Lei Y, Fuchs D, Allen JE, Zaslavskaia LA, MacBeath G. PDZ domain binding selectivity is optimized across the mouse proteome. Science 2007; 317:364-9; PMID:17641200; http://dx.doi.org/10.1126/science.1144592
  • Furuse M, Sasaki H, Tsukita S. Manner of interaction of heterogeneous claudin species within and between tight junction strands. J Cell Biol 1999; 147:891-903; PMID:10562289; http://dx.doi.org/10.1083/jcb.147.4.891
  • Lim TS, Vedula SR, Hunziker W, Lim CT. Kinetics of adhesion mediated by extracellular loops of claudin-2 as revealed by single-molecule force spectroscopy. J Mol Biol 2008; 381:681-91; PMID:18635194; http://dx.doi.org/10.1016/j.jmb.2008.06.009
  • Van Itallie CM, Colegio OR, Anderson JM. The cytoplasmic tails of claudins can influence tight junction barrier properties through effects on protein stability. J Membr Biol 2004; 199:29-38; PMID:15366421; http://dx.doi.org/10.1007/s00232-004-0673-z
  • Angelow S, Yu AS. Cysteine mutagenesis to study the structure of claudin-2 paracellular pores. Ann N Y Acad Sci 2009; 1165:143-7; PMID:19538299; http://dx.doi.org/10.1111/j.1749-6632.2009.04038.x
  • Yu AS, Cheng MH, Angelow S, Gunzel D, Kanzawa SA, Schneeberger EE, Fromm M, Coalson RD. Molecular basis for cation selectivity in claudin-2-based paracellular pores: identification of an electrostatic interaction site. J Gen Physiol 2009; 133:111-27; PMID:19114638; http://dx.doi.org/10.1085/jgp.200810154
  • Angelow S, Ahlstrom R, Yu AS. Biology of claudins. Am J Physiol Renal Physiol 2008; 295:F867-76; PMID:18480174; http://dx.doi.org/10.1152/ajprenal.90264.2008
  • Li J, Angelow S, Linge A, Zhuo M, Yu AS. Claudin-2 pore function requires an intramolecular disulfide bond between two conserved extracellular cysteines. Am J Physiol Cell Physiol 2013; 305:C190-6; PMID:23677799; http://dx.doi.org/10.1152/ajpcell.00074.2013
  • Li J, Zhuo M, Pei L, Rajagopal M, Yu AS. Comprehensive cysteine-scanning mutagenesis reveals claudin-2 pore-lining residues with different intrapore locations. J Biol Chem 2014; 289:6475-84P; PMID:24436330
  • Li J, Zhuo M, Pei L, Yu AS. Conserved aromatic residue confers cation selectivity in claudin-2 and claudin-10b. J Biol Chem 2013; 288:22790-7; PMID:23760508; http://dx.doi.org/10.1074/jbc.M113.484238
  • Inai T, Sengoku A, Hirose E, Iida H, Shibata Y. Comparative characterization of mouse rectum CMT93-I and -II cells by expression of claudin isoforms and tight junction morphology and function. Histochem Cell Biol 2008; 129:223-32; PMID:18034259; http://dx.doi.org/10.1007/s00418-007-0360-0
  • Anderson JM, Van Itallie CM, Fanning AS. Setting up a selective barrier at the apical junction complex. Curr Opin Cell Biol 2004; 16:140-5; PMID:15196556; http://dx.doi.org/10.1016/j.ceb.2004.01.005
  • Furuse M, Furuse K, Sasaki H, Tsukita S. Conversion of zonulae occludentes from tight to leaky strand type by introducing claudin-2 into Madin-Darby canine kidney I cells. J Cell Biol 2001; 153:263-72; PMID:11309408; http://dx.doi.org/10.1083/jcb.153.2.263
  • Singh AB, Sugimoto K, Dhawan P, Harris RC. Juxtacrine activation of EGFR regulates claudin expression and increases transepithelial resistance. Am J Physiol Cell Physiol 2007; 293:C1660-8; PMID:17855771; http://dx.doi.org/10.1152/ajpcell.00274.2007
  • Enck AH, Berger UV, Yu AS. Claudin-2 is selectively expressed in proximal nephron in mouse kidney. Am J Physiol Renal Physiol 2001; 281:F966-74; PMID:11592954
  • Kiuchi-Saishin Y, Gotoh S, Furuse M, Takasuga A, Tano Y, Tsukita S. Differential expression patterns of claudins, tight junction membrane proteins, in mouse nephron segments. J Am Soc Nephrol 2002; 13:875-86; PMID:11912246
  • Lameris AL, Huybers S, Kaukinen K, Makela TH, Bindels RJ, Hoenderop JG, Nevalainen PI. Expression profiling of claudins in the human gastrointestinal tract in health and during inflammatory bowel disease. Scand J Gastroenterol 2013; 48:58-69; PMID:23205909; http://dx.doi.org/10.3109/00365521.2012.741616
  • Escaffit F, Boudreau F, Beaulieu JF. Differential expression of claudin-2 along the human intestine: implication of GATA-4 in the maintenance of claudin-2 in differentiating cells. J Cell Physiol 2005; 203:15-26; PMID:15389642; http://dx.doi.org/10.1002/jcp.20189
  • Tamura A, Hayashi H, Imasato M, Yamazaki Y, Hagiwara A, Wada M, Noda T, Watanabe M, Suzuki Y, Tsukita S. Loss of claudin-15, but not claudin-2, causes Na+ deficiency and glucose malabsorption in mouse small intestine. Gastroenterology 2011; 140:913-23; PMID:20727355; http://dx.doi.org/10.1053/j.gastro.2010.08.006
  • Suzuki H, Nishizawa T, Tani K, Yamazaki Y, Tamura A, Ishitani R, Dohmae N, Tsukita S, Nureki O, Fujiyoshi Y. Crystal structure of a claudin provides insight into the architecture of tight junctions. Science 2014; 344:304-7; PMID:24744376; http://dx.doi.org/10.1126/science.1248571
  • Gunzel D, Fromm M. Claudins and other tight junction proteins. Compr Physiol 2012; 2:1819-52; PMID:23723025
  • Amasheh S, Dullat S, Fromm M, Schulzke JD, Buhr HJ, Kroesen AJ. Inflamed pouch mucosa possesses altered tight junctions indicating recurrence of inflammatory bowel disease. Int J Colorectal Dis 2009; 24:1149-56; PMID:19488769; http://dx.doi.org/10.1007/s00384-009-0737-8
  • Prasad S, Mingrino R, Kaukinen K, Hayes KL, Powell RM, MacDonald TT, Collins JE. Inflammatory processes have differential effects on claudins 2, 3 and 4 in colonic epithelial cells. Lab Invest 2005; 85:1139-62; PMID:16007110; http://dx.doi.org/10.1038/labinvest.3700316
  • Zeissig S, Burgel N, Gunzel D, Richter J, Mankertz J, Wahnschaffe U, Kroesen AJ, Zeitz M, Fromm M, Schulzke JD. 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 2007; 56:61-72; PMID:16822808; http://dx.doi.org/10.1136/gut.2006.094375
  • Heller F, Fromm A, Gitter AH, Mankertz J, Schulzke JD. Epithelial apoptosis is a prominent feature of the epithelial barrier disturbance in intestinal inflammation: effect of pro-inflammatory interleukin-13 on epithelial cell function. Mucosal Immunol 2008; 1 Suppl 1:S58-61; PMID:19079233; http://dx.doi.org/10.1038/mi.2008.46
  • Mankertz J, Amasheh M, Krug SM, Fromm A, Amasheh S, Hillenbrand B, Tavalali S, Fromm M, Schulzke JD. TNFalpha up-regulates claudin-2 expression in epithelial HT-29/B6 cells via phosphatidylinositol-3-kinase signaling. Cell Tissue Res 2009; 336:67-77; PMID:19214581; http://dx.doi.org/10.1007/s00441-009-0751-8
  • Suzuki T, Yoshinaga N, Tanabe S. Interleukin-6 (IL-6) regulates claudin-2 expression and tight junction permeability in intestinal epithelium. J Biol Chem 2011; 286:31263-71; PMID:21771795; http://dx.doi.org/10.1074/jbc.M111.238147
  • Amasheh M, Fromm A, Krug SM, Amasheh S, Andres S, Zeitz M, Fromm M, Schulzke JD. TNFalpha-induced and berberine-antagonized tight junction barrier impairment via tyrosine kinase, Akt and NFkappaB signaling. J Cell Sci 2010; 123:4145-55; PMID:21062898; http://dx.doi.org/10.1242/jcs.070896
  • Kinugasa T, Sakaguchi T, Gu X, Reinecker HC. Claudins regulate the intestinal barrier in response to immune mediators. Gastroenterology 2000; 118:1001-11; PMID:10833473; http://dx.doi.org/10.1016/S0016-5085(00)70351-9
  • Sakaguchi T, Gu X, Golden HM, Suh E, Rhoads DB, Reinecker HC. Cloning of the human claudin-2 5'-flanking region revealed a TATA-less promoter with conserved binding sites in mouse and human for caudal-related homeodomain proteins and hepatocyte nuclear factor-1alpha. J Biol Chem 2002; 277:21361-70; PMID:11934881; http://dx.doi.org/10.1074/jbc.M110261200
  • Mankertz J, Hillenbrand B, Tavalali S, Huber O, Fromm M, Schulzke JD. Functional crosstalk between Wnt signaling and Cdx-related transcriptional activation in the regulation of the claudin-2 promoter activity. Biochem Biophys Res Commun 2004; 314:1001-7; PMID:14751232; http://dx.doi.org/10.1016/j.bbrc.2003.12.185
  • Boudreau F, Rings EH, van Wering HM, Kim RK, Swain GP, Krasinski SD, Moffett J, Grand RJ, Suh ER, Traber PG. Hepatocyte nuclear factor-1 alpha, GATA-4, and caudal related homeodomain protein Cdx2 interact functionally to modulate intestinal gene transcription. Implication for the developmental regulation of the sucrase-isomaltase gene. J Biol Chem 2002; 277:31909-17; PMID:12060663; http://dx.doi.org/10.1074/jbc.M204622200
  • Al-Sadi R, Ye D, Boivin M, Guo S, Hashimi M, Ereifej L, Ma TY. Interleukin-6 modulation of intestinal epithelial tight junction permeability is mediated by JNK pathway activation of claudin-2 gene. PLoS One 2014; 9:e85345; PMID:24662742; http://dx.doi.org/10.1371/journal.pone.0085345
  • Rosen MJ, Frey MR, Washington MK, Chaturvedi R, Kuhnhein LA, Matta P, Revetta FL, Wilson KT, Polk DB. STAT6 activation in ulcerative colitis: a new target for prevention of IL-13-induced colon epithelial cell dysfunction. Inflamm Bowel Dis 2011; 17:2224-34; PMID:21308881; http://dx.doi.org/10.1002/ibd.21628
  • Rosen MJ, Chaturvedi R, Washington MK, Kuhnhein LA, Moore PD, Coggeshall SS, McDonough EM, Weitkamp JH, Singh AB, Coburn LA, et al. STAT6 deficiency ameliorates severity of oxazolone colitis by decreasing expression of claudin-2 and Th2-inducing cytokines. J Immunol 2013; 190:1849-58; PMID:23303670; http://dx.doi.org/10.4049/jimmunol.1201373
  • Weber CR, Raleigh DR, Su L, Shen L, Sullivan EA, Wang Y, Turner JR. Epithelial myosin light chain kinase activation induces mucosal interleukin-13 expression to alter tight junction ion selectivity. J Biol Chem 2010; 285:12037-46; PMID:20177070; http://dx.doi.org/10.1074/jbc.M109.064808
  • Mazzon E, Cuzzocrea S. Absence of functional peroxisome proliferator-activated receptor-alpha enhanced ileum permeability during experimental colitis. Shock 2007; 28:192-201; PMID:17515853; http://dx.doi.org/10.1097/SHK.0b013e318033eb29
  • González-Mariscal L, Garay E, Quirós M. Regulation of claudins by posttranslational modifications and cell-signaling cascades. Curr Top Membr 65: 113-150, 2010.
  • Van Itallie CM, Tietgens AJ, LoGrande K, Aponte A, Gucek M, Anderson JM. Phosphorylation of claudin-2 on serine 208 promotes membrane retention and reduces trafficking to lysosomes. J Cell Sci 2012; 125:4902-12; PMID:22825868; http://dx.doi.org/10.1242/jcs.111237
  • Van Itallie CM, Mitic LL, Anderson JM. SUMOylation of claudin-2. Ann N Y Acad Sci 2012; 1258:60-4; PMID:22731716; http://dx.doi.org/10.1111/j.1749-6632.2012.06541.x
  • Angelow S, Schneeberger EE, Yu AS. Claudin-8 expression in renal epithelial cells augments the paracellular barrier by replacing endogenous claudin-2. J Membr Biol 2007; 215:147-59; PMID:17516019; http://dx.doi.org/10.1007/s00232-007-9014-3
  • Yu AS, Enck AH, Lencer WI, Schneeberger EE. Claudin-8 expression in Madin-Darby canine kidney cells augments the paracellular barrier to cation permeation. J Biol Chem 2003; 278:17350-9; PMID:12615928; http://dx.doi.org/10.1074/jbc.M213286200
  • Epple HJ, Zeitz M. Intestinal mucosal barrier function in HIV infection. Ann. N.Y. Acad. Sci. 2012; 1258:19-24.
  • Heller F, Florian P, Bojarski C, Richter J, Christ M, Hillenbrand B, Mankertz J, Gitter AH, Burgel N, Fromm M, et al. Interleukin-13 is the key effector Th2 cytokine in ulcerative colitis that affects epithelial tight junctions, apoptosis, and cell restitution. Gastroenterology 2005; 129:550-64; PMID:16083712; http://dx.doi.org/10.1016/j.gastro.2005.05.002
  • Oshima T, Miwa H, Joh T. Changes in the expression of claudins in active ulcerative colitis. J Gastroenterol Hepatol 2008; 23 Suppl 2:S146-50; PMID:19120888; http://dx.doi.org/10.1111/j.1440-1746.2008.05405.x
  • Schumann M, Gunzel D, Buergel N, Richter JF, Troeger H, May C, Fromm A, Sorgenfrei D, Daum S, Bojarski C, et al. Cell polarity-determining proteins Par-3 and PP-1 are involved in epithelial tight junction defects in coeliac disease. Gut 2011; 61:220-8; PMID:21865402; http://dx.doi.org/10.1136/gutjnl-2011-300123
  • Das P, Goswami P, Das TK, Nag T, Sreenivas V, Ahuja V, Panda SK, Gupta SD, Makharia GK. Comparative tight junction protein expressions in colonic Crohn's disease, ulcerative colitis, and tuberculosis: a new perspective. Virchows Arch 2012; 460:261-70; PMID:22297703; http://dx.doi.org/10.1007/s00428-012-1195-1
  • Marchiando AM, Shen L, Graham WV, Weber CR, Schwarz BT, Austin JR 2nd, Raleigh DR, Guan Y, Watson AJ, Montrose MH, et al. Caveolin-1-dependent occludin endocytosis is required for TNF-induced tight junction regulation in vivo. J Cell Biol 2010; 189:111-26; PMID:20351069; http://dx.doi.org/10.1083/jcb.200902153
  • Desreumaux P, Brandt E, Gambiez L, Emilie D, Geboes K, Klein O, Ectors N, Cortot A, Capron M, Colombel JF. Distinct cytokine patterns in early and chronic ileal lesions of Crohn's disease. Gastroenterology 1997; 113:118-26; PMID:9207269; http://dx.doi.org/10.1016/S0016-5085(97)70116-1
  • Knutson L, Ahrenstedt O, Odlind B, Hallgren R. The jejunal secretion of histamine is increased in active Crohn's disease. Gastroenterology 1990; 98:849-54; PMID:1690156; http://dx.doi.org/10.1016/0016-5085(90)90006-M
  • Zorzi F, Monteleone I, Sarra M, Calabrese E, Marafini I, Cretella M, Sedda S, Biancone L, Pallone F, Monteleone G. Distinct profiles of effector cytokines mark the different phases of Crohn's disease. PLoS One 2013; 8:e54562; PMID:23349929; http://dx.doi.org/10.1371/journal.pone.0054562
  • Andoh A, Zhang Z, Inatomi O, Fujino S, Deguchi Y, Araki Y, Tsujikawa T, Kitoh K, Kim-Mitsuyama S, Takayanagi A, et al. Interleukin-22, a member of the IL-10 subfamily, induces inflammatory responses in colonic subepithelial myofibroblasts. Gastroenterology 2005; 129:969-84; PMID:16143135; http://dx.doi.org/10.1053/j.gastro.2005.06.071
  • Brand S, Beigel F, Olszak T, Zitzmann K, Eichhorst ST, Otte JM, Diepolder H, Marquardt A, Jagla W, Popp A, et al. IL-22 is increased in active Crohn's disease and promotes proinflammatory gene expression and intestinal epithelial cell migration. Am J Physiol Gastrointest Liver Physiol 2006; 290:G827-38; PMID:16537974; http://dx.doi.org/10.1152/ajpgi.00513.2005
  • John LJ, Fromm M, Schulzke JD. Epithelial barriers in intestinal inflammation. Antioxid Redox Signal 2011; 15:1255-70; PMID:21294654; http://dx.doi.org/10.1089/ars.2011.3892
  • Amasheh M, Grotjohann I, Amasheh S, Fromm A, Soderholm JD, Zeitz M, Fromm M, Schulzke JD. 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 Gastroenterol 2009; 44:1226-35; PMID:19658020; http://dx.doi.org/10.1080/00365520903131973
  • Blair SA, Kane SV, Clayburgh DR, Turner JR. Epithelial myosin light chain kinase expression and activity are upregulated in inflammatory bowel disease. Lab Invest 2006; 86:191-201; PMID:16402035; http://dx.doi.org/10.1038/labinvest.3700373
  • Al-Sadi R, Ye D, Said HM, Ma TY. Cellular and molecular mechanism of interleukin-1beta modulation of Caco-2 intestinal epithelial tight junction barrier. J Cell Mol Med 2011; 15:970-82; PMID:20406328; http://dx.doi.org/10.1111/j.1582-4934.2010.01065.x
  • Ye D, Ma TY. Cellular and molecular mechanisms that mediate basal and tumour necrosis factor-alpha-induced regulation of myosin light chain kinase gene activity. J Cell Mol Med 2008; 12:1331-46; PMID:18363837; http://dx.doi.org/10.1111/j.1582-4934.2008.00302.x
  • Shen L, Black ED, Witkowski ED, Lencer WI, Guerriero V, Schneeberger EE, Turner JR. Myosin light chain phosphorylation regulates barrier function by remodeling tight junction structure. J Cell Sci 2006; 119:2095-106; PMID:16638813; http://dx.doi.org/10.1242/jcs.02915
  • Bruewer M, Utech M, Ivanov AI, Hopkins AM, Parkos CA, Nusrat A. Interferon-gamma induces internalization of epithelial tight junction proteins via a macropinocytosis-like process. Faseb J 2005; 19:923-33; PMID:15923402; http://dx.doi.org/10.1096/fj.04-3260com
  • Irvine EJ, Marshall JK. Increased intestinal permeability precedes the onset of Crohn's disease in a subject with familial risk. Gastroenterology 2000; 119:1740-4; PMID:11113095; http://dx.doi.org/10.1053/gast.2000.20231
  • Wyatt J, Vogelsang H, Hubl W, Waldhoer T, Lochs H. Intestinal permeability and the prediction of relapse in Crohn's disease. Lancet 1993; 341:1437-9; PMID:8099141; http://dx.doi.org/10.1016/0140-6736(93)90882-H
  • Lala S, Ogura Y, Osborne C, Hor SY, Bromfield A, Davies S, Ogunbiyi O, Nunez G, Keshav S. Crohn's disease and the NOD2 gene: a role for paneth cells. Gastroenterology 2003; 125:47-57; PMID:12851870; http://dx.doi.org/10.1016/S0016-5085(03)00661-9
  • Buhner S, Buning C, Genschel J, Kling K, Herrmann D, Dignass A, Kuechler I, Krueger S, Schmidt HH, Lochs H. Genetic basis for increased intestinal permeability in families with Crohn's disease: role of CARD15 3020insC mutation? Gut 2006; 55:342-7; PMID:16000642; http://dx.doi.org/10.1136/gut.2005.065557
  • D'Inca R, Annese V, di Leo V, Latiano A, Quaino V, Abazia C, Vettorato MG, Sturniolo GC. Increased intestinal permeability and NOD2 variants in familial and sporadic Crohn's disease. Aliment Pharmacol Ther 2006; 23:1455-61; PMID:16669960; http://dx.doi.org/10.1111/j.1365-2036.2006.02916.x
  • Voss E, Wehkamp J, Wehkamp K, Stange EF, Schroder JM, Harder J. NOD2/CARD15 mediates induction of the antimicrobial peptide human beta-defensin-2. J Biol Chem 2006; 281:2005-11; PMID:16319062; http://dx.doi.org/10.1074/jbc.M511044200
  • Wehkamp J, Harder J, Weichenthal M, Schwab M, Schaffeler E, Schlee M, Herrlinger KR, Stallmach A, Noack F, Fritz P, et al. NOD2 (CARD15) mutations in Crohn's disease are associated with diminished mucosal alpha-defensin expression. Gut 2004; 53:1658-64; PMID:15479689; http://dx.doi.org/10.1136/gut.2003.032805
  • Rosenstiel P, Fantini M, Brautigam K, Kuhbacher T, Waetzig GH, Seegert D, Schreiber S. TNF-alpha and IFN-gamma regulate the expression of the NOD2 (CARD15) gene in human intestinal epithelial cells. Gastroenterology 2003; 124:1001-9; PMID:12671897; http://dx.doi.org/10.1053/gast.2003.50157
  • Bucker R, Troeger H, Kleer J, Fromm M, Schulzke JD. Arcobacter butzleri induces barrier dysfunction in intestinal HT-29/B6 cells. J Infect Dis 2009; 200:756-64; PMID:19604116; http://dx.doi.org/10.1086/600868
  • Hering NA, Richter JF, Krug SM, Gunzel D, Fromm A, Bohn E, Rosenthal R, Bucker R, Fromm M, Troeger H, et al. Yersinia enterocolitica induces epithelial barrier dysfunction through regional tight junction changes in colonic HT-29/B6 cell monolayers. Lab Invest 2011; 91:310-24; PMID:20956974; http://dx.doi.org/10.1038/labinvest.2010.180
  • Barreau F, Meinzer U, Chareyre F, Berrebi D, Niwa-Kawakita M, Dussaillant M, Foligne B, Ollendorff V, Heyman M, Bonacorsi S, et al. CARD15/NOD2 is required for Peyer's patches homeostasis in mice. PLoS One 2007; 2:e523; PMID:17565376; http://dx.doi.org/10.1371/journal.pone.0000523
  • Wisner DM, Harris LR 3rd, Green CL, Poritz LS. Opposing regulation of the tight junction protein claudin-2 by interferon-gamma and interleukin-4. J Surg Res 2008; 144:1-7; PMID:17640674; http://dx.doi.org/10.1016/j.jss.2007.03.059
  • Olson TS, Reuter BK, Scott KG, Morris MA, Wang XM, Hancock LN, Burcin TL, Cohn SM, Ernst PB, Cominelli F, et al. The primary defect in experimental ileitis originates from a nonhematopoietic source. J Exp Med 2006; 203:541-52; PMID:16505137; http://dx.doi.org/10.1084/jem.20050407
  • Gitter AH, Wullstein F, Fromm M, Schulzke JD. Epithelial barrier defects in ulcerative colitis: characterization and quantification by electrophysiological imaging. Gastroenterology 2001; 121:1320-8; PMID:11729111; http://dx.doi.org/10.1053/gast.2001.29694
  • Schmitz H, Barmeyer C, Fromm M, Runkel N, Foss HD, Bentzel CJ, Riecken EO, Schulzke JD. Altered tight junction structure contributes to the impaired epithelial barrier function in ulcerative colitis. Gastroenterology 1999; 116:301-9; PMID:9922310; http://dx.doi.org/10.1016/S0016-5085(99)70126-5
  • Bojarski C, Gitter AH, Bendfeldt K, Mankertz J, Schmitz H, Wagner S, Fromm M, Schulzke JD. Permeability of human HT-29/B6 colonic epithelium as a function of apoptosis. J Physiol 2001; 535:541-52; PMID:11533143; http://dx.doi.org/10.1111/j.1469-7793.2001.00541.x
  • Gitter AH, Bendfeldt K, Schulzke JD, Fromm M. Leaks in the epithelial barrier caused by spontaneous and TNF-alpha-induced single-cell apoptosis. Faseb J 2000; 14:1749-53; PMID:10973924; http://dx.doi.org/10.1096/fj.99-0898com
  • Ahn SH, Shah YM, Inoue J, Morimura K, Kim I, Yim S, Lambert G, Kurotani R, Nagashima K, Gonzalez FJ, et al. Hepatocyte nuclear factor 4alpha in the intestinal epithelial cells protects against inflammatory bowel disease. Inflamm Bowel Dis 2008; 14:908-20; PMID:18338782; http://dx.doi.org/10.1002/ibd.20413
  • Cattin AL, Le Beyec J, Barreau F, Saint-Just S, Houllier A, Gonzalez FJ, Robine S, Pincon-Raymond M, Cardot P, Lacasa M, et al. Hepatocyte nuclear factor 4alpha, a key factor for homeostasis, cell architecture, and barrier function of the adult intestinal epithelium. Mol Cell Biol 2009; 29:6294-308; PMID:19805521; http://dx.doi.org/10.1128/MCB.00939-09
  • Visser J, Rozing J, Sapone A, Lammers K, Fasano A. Tight junctions, intestinal permeability, and autoimmunity: celiac disease and type 1 diabetes paradigms. Ann N Y Acad Sci 2009; 1165:195-205; PMID:19538307; http://dx.doi.org/10.1111/j.1749-6632.2009.04037.x
  • Matysiak-Budnik T, Candalh C, Dugave C, Namane A, Cellier C, Cerf-Bensussan N, Heyman M. Alterations of the intestinal transport and processing of gliadin peptides in celiac disease. Gastroenterology 2003; 125:696-707; PMID:12949716; http://dx.doi.org/10.1016/S0016-5085(03)01049-7
  • Schumann M, Richter JF, Wedell I, Moos V, Zimmermann-Kordmann M, Schneider T, Daum S, Zeitz M, Fromm M, Schulzke JD. Mechanisms of epithelial translocation of the alpha(2)-gliadin-33mer in coeliac sprue. Gut 2008; 57:747-54; PMID:18305066
  • Ciccocioppo R, Finamore A, Ara C, Di Sabatino A, Mengheri E, Corazza GR. Altered expression, localization, and phosphorylation of epithelial junctional proteins in celiac disease. Am J Clin Pathol 2006; 125:502-11; PMID:16627260; http://dx.doi.org/10.1309/DTYRA91G8R0KTM8M
  • Schumann M, Kamel S, Pahlitzsch ML, Lebenheim L, May C, Krauss M, Hummel M, Daum S, Fromm M, Schulzke JD. Defective tight junctions in refractory celiac disease. Ann N Y Acad Sci 2012; 1258:43-51; PMID:22731714; http://dx.doi.org/10.1111/j.1749-6632.2012.06565.x
  • Szakal DN, Gyorffy H, Arato A, Cseh A, Molnar K, Papp M, Dezsofi A, Veres G. Mucosal expression of claudins 2, 3 and 4 in proximal and distal part of duodenum in children with coeliac disease. Virchows Arch 2010; 456:245-50; PMID:20143085; http://dx.doi.org/10.1007/s00428-009-0879-7
  • van Elburg RM, Uil JJ, Mulder CJ, Heymans HS. Intestinal permeability in patients with coeliac disease and relatives of patients with coeliac disease. Gut 1993; 34:354-7; PMID:8472983; http://dx.doi.org/10.1136/gut.34.3.354
  • Menard S, Lebreton C, Schumann M, Matysiak-Budnik T, Dugave C, Bouhnik Y, Malamut G, Cellier C, Allez M, Crenn P, et al. Paracellular versus transcellular intestinal permeability to gliadin peptides in active celiac disease. Am J Pathol 2012; 180:608-15; PMID:22119716; http://dx.doi.org/10.1016/j.ajpath.2011.10.019
  • Kohl D, Ashkenazi A, Ben-Shaul Y, Bacher A. Tight junctions of jejunal surface and crypt cells in celiac disease: a freeze-fracture study. J Pediatr Gastroenterol Nutr 1987; 6:57-65; PMID:3794934
  • Schulzke JD, Bentzel CJ, Schulzke I, Riecken EO, Fromm M. Epithelial tight junction structure in the jejunum of children with acute and treated celiac sprue. Pediatr Res 1998; 43:435-41; PMID:9544995; http://dx.doi.org/10.1203/00006450-199804000-00001
  • Utech M, Ivanov AI, Samarin SN, Bruewer M, Turner JR, Mrsny RJ, Parkos CA, Nusrat A. Mechanism of IFN-gamma-induced endocytosis of tight junction proteins: myosin II-dependent vacuolarization of the apical plasma membrane. Mol Biol Cell 2005; 16:5040-52; PMID:16055505; http://dx.doi.org/10.1091/mbc.E05-03-0193
  • Brenchley JM, Price DA, Schacker TW, Asher TE, Silvestri G, Rao S, Kazzaz Z, Bornstein E, Lambotte O, Altmann D, et al. Microbial translocation is a cause of systemic immune activation in chronic HIV infection. Nat Med 2006; 12:1365-71; PMID:17115046; http://dx.doi.org/10.1038/nm1511
  • Brenchley JM, Schacker TW, Ruff LE, Price DA, Taylor JH, Beilman GJ, Nguyen PL, Khoruts A, Larson M, Haase AT, et al. CD4+ T cell depletion during all stages of HIV disease occurs predominantly in the gastrointestinal tract. J Exp Med 2004; 200:749-59; PMID:15365096; http://dx.doi.org/10.1084/jem.20040874
  • Epple HJ, Allers K, Troger H, Kuhl A, Erben U, Fromm M, Zeitz M, Loddenkemper C, Schulzke JD, Schneider T. Acute HIV infection induces mucosal infiltration with CD4+ and CD8+ T cells, epithelial apoptosis, and a mucosal barrier defect. Gastroenterology 2010; 139:1289-300; PMID:20600014; http://dx.doi.org/10.1053/j.gastro.2010.06.065
  • Epple HJ, Schneider T, Troeger H, Kunkel D, Allers K, Moos V, Amasheh M, Loddenkemper C, Fromm M, Zeitz M, et al. Impairment of the intestinal barrier is evident in untreated but absent in suppressively treated HIV-infected patients. Gut 2009; 58:220-7; PMID:18936106; http://dx.doi.org/10.1136/gut.2008.150425
  • Nazli A, Chan O, Dobson-Belaire WN, Ouellet M, Tremblay MJ, Gray-Owen SD, Arsenault AL, Kaushic C. Exposure to HIV-1 directly impairs mucosal epithelial barrier integrity allowing microbial translocation. PLoS Pathog 2010; 6:e1000852; PMID:20386714; http://dx.doi.org/10.1371/journal.ppat.1000852
  • Sankaran S, George MD, Reay E, Guadalupe M, Flamm J, Prindiville T, Dandekar S. Rapid onset of intestinal epithelial barrier dysfunction in primary human immunodeficiency virus infection is driven by an imbalance between immune response and mucosal repair and regeneration. J Virol 2008; 82:538-45; PMID:17959677; http://dx.doi.org/10.1128/JVI.01449-07
  • Fackler OT, Schafer M, Schmidt W, Zippel T, Heise W, Schneider T, Zeitz M, Riecken EO, Mueller-Lantzsch N, Ullrich R. HIV-1 p24 but not proviral load is increased in the intestinal mucosa compared with the peripheral blood in HIV-infected patients. Aids 1998; 12:139-46; PMID:9468362; http://dx.doi.org/10.1097/00002030-199802000-00003
  • Mattapallil JJ, Douek DC, Hill B, Nishimura Y, Martin M, Roederer M. Massive infection and loss of memory CD4+ T cells in multiple tissues during acute SIV infection. Nature 2005; 434:1093-7; PMID:15793563; http://dx.doi.org/10.1038/nature03501
  • Buccigrossi V, Laudiero G, Nicastro E, Miele E, Esposito F, Guarino A. The HIV-1 transactivator factor (Tat) induces enterocyte apoptosis through a redox-mediated mechanism. PLoS One 2011; 6:e29436; PMID:22216281; http://dx.doi.org/10.1371/journal.pone.0029436
  • Clayton F, Kotler DP, Kuwada SK, Morgan T, Stepan C, Kuang J, Le J, Fantini J. Gp120-induced Bob/GPR15 activation: a possible cause of human immunodeficiency virus enteropathy. Am J Pathol 2001; 159:1933-9; PMID:11696454; http://dx.doi.org/10.1016/S0002-9440(10)63040-4
  • Quigley MA, Kamali A, Kinsman J, Kamulegeya I, Nakiyingi-Miiro J, Kiwuwa S, Kengeya-Kayondo JF, Carpenter LM, Whitworth JA. The impact of attending a behavioural intervention on HIV incidence in Masaka, Uganda. Aids 2004; 18:2055-63; PMID:15577627; http://dx.doi.org/10.1097/00002030-200410210-00010
  • Shacklett BL, Cox CA, Quigley MF, Kreis C, Stollman NH, Jacobson MA, Andersson J, Sandberg JK, Nixon DF. Abundant expression of granzyme A, but not perforin, in granules of CD8+ T cells in GALT: implications for immune control of HIV-1 infection. J Immunol 2004; 173:641-8; PMID:15210827; http://dx.doi.org/10.4049/jimmunol.173.1.641
  • Kim CJ, Nazli A, Rojas OL, Chege D, Alidina Z, Huibner S, Mujib S, Benko E, Kovacs C, Shin LY, et al. A role for mucosal IL-22 production and Th22 cells in HIV-associated mucosal immunopathogenesis. Mucosal Immunol 2012; 5:670-80; PMID:22854709; http://dx.doi.org/10.1038/mi.2012.72
  • Fischer A, Gluth M, Pape UF, Wiedenmann B, Theuring F, Baumgart DC. Adalimumab prevents barrier dysfunction and antagonizes distinct effects of TNF-alpha on tight junction proteins and signaling pathways in intestinal epithelial cells. Am J Physiol Gastrointest Liver Physiol 2013; 304:G970-9; PMID:23538493; http://dx.doi.org/10.1152/ajpgi.00183.2012
  • Vieira EL, Leonel AJ, Sad AP, Beltrao NR, Costa TF, Ferreira TM, Gomes-Santos AC, Faria AM, Peluzio MC, Cara DC, et al. Oral administration of sodium butyrate attenuates inflammation and mucosal lesion in experimental acute ulcerative colitis. J Nutr Biochem 2012; 23:430-6; PMID:21658926; http://dx.doi.org/10.1016/j.jnutbio.2011.01.007
  • Daly K, Shirazi-Beechey SP. Microarray analysis of butyrate regulated genes in colonic epithelial cells. DNA Cell Biol 2006; 25:49-62; PMID:16405400; http://dx.doi.org/10.1089/dna.2006.25.49
  • Ploger S, Stumpff F, Penner GB, Schulzke JD, Gabel G, Martens H, Shen Z, Gunzel D, Aschenbach JR. Microbial butyrate and its role for barrier function in the gastrointestinal tract. Ann N Y Acad Sci 2012; 1258:52-9; PMID:22731715; http://dx.doi.org/10.1111/j.1749-6632.2012.06553.x
  • Zhang Q, Piao XL, Piao XS, Lu T, Wang D, Kim SW. Preventive effect of Coptis chinensis and berberine on intestinal injury in rats challenged with lipopolysaccharides. Food Chem Toxicol 2011; 49:61-9; PMID:20932871; http://dx.doi.org/10.1016/j.fct.2010.09.032
  • Wang N, Yu H, Ma J, Wu W, Zhao D, Shi X, Tian H, Jiang H. Evidence for tight junction protein disruption in intestinal mucosa of malignant obstructive jaundice patients. Scand J Gastroenterol 2010; 45:191-9; PMID:20095884; http://dx.doi.org/10.3109/00365520903406701
  • Burgel N, Bojarski C, Mankertz J, Zeitz M, Fromm M, Schulzke JD. Mechanisms of diarrhea in collagenous colitis. Gastroenterology 2002; 123:433-43; PMID:12145796; http://dx.doi.org/10.1053/gast.2002.34784

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.