nach oben

Erschienen in:

01.12.2011 | Original Article

Pathophysiological Investigation of the Gastric Surface Mucous Gel Layer of Patients with Helicobacter pylori Infection by Using Immunoassays for Trefoil Factor Family 2 and Gastric Gland Mucous Cell-Type Mucin in Gastric Juice

verfasst von: Seiko Kubota, Kazuyoshi Yamauchi, Mitsutoshi Sugano, Kenji Kawasaki, Atsushi Sugiyama, Kenji Matsuzawa, Taiji Akamatsu, Yasukazu Ohmoto, Hiroyoshi Ota

Erschienen in: Digestive Diseases and Sciences | Ausgabe 12/2011

Einloggen, um Zugang zu erhalten

Abstract

Background

The trefoil factor family (TFF) 2 protein is produced by gastric gland mucous cells (GMCs), and the secreted TFF2 shares a mucosal barrier function with GMC-type mucin. Recently, we presented an enzyme-linked immunosorbent assay (ELISA) method for measurement of GMC-type mucin in the gastric juice.

Aims

We aimed to develop an ELISA for TFF2 and to assess pathophysiological changes in the gastric surface mucous gel layer (SMGL) of patients with Helicobacter pylori infection.

Methods

The distribution of TFF2 and GMC-type mucin in the SMGL was immunohistochemically determined. The ELISA for TFF2 was based on a polyclonal goat antibody. Recombinant TFF2 was employed to prepare the calibrators. TFF2 and GMC-type mucin in the gastric juice in healthy individuals (n = 33) and patients with gastritis (n = 37), gastric ulcer (n = 16), and duodenal ulcer (n = 10) were assayed using ELISA.

Results

TFF2 and GMC-type mucin were immunohistochemically co-localized in the gastric SMGL and GMCs. The TFF2 levels in the patients were significantly higher than those in the healthy individuals. Further, the TFF2 levels in the H. pylori-positive patients were significantly higher than those in the H. pylori-negative patients, and decreased after the eradication of the infection. GMC-type mucin levels showed a tendency similar to that of TFF2 levels.

Conclusions

The upregulation of TFF2 and GMC-type mucin secretion may reflect the response of the gastric mucosa to H. pylori-induced injuries. TFF2 and GMC-type mucin secreted into the SMGL may protect the gastric mucosa against H. pylori.

Ota H, Katsuyama T, Ishii K, Nakayama J, Shiozawa T, Tsukahara Y. A dual staining method for identifying mucins of different gastric epithelial mucous cells. Histochem J. 1991;23:22–28.PubMedCrossRef

Ota H, Katsuyama T. Alternating laminated array of two types of mucin in the human gastric surface mucous layer. Histochem J. 1992;24:86–92.PubMedCrossRef

Ho SB, Takamura K, Anway R, Shekels LL, Toribara NW, Ota H. The adherent gastric mucous layer is composed of alternating layers of MUC5AC and MUC6 mucin proteins. Dig Dis Sci. 2004;49:1598–1606.PubMedCrossRef

Tomasetto C, Rio MC, Gautier C, et al. hSP, the domain-duplicated homolog of pS2 protein, is co-expressed with pS2 in stomach but not in breast carcinoma. EMBO J. 1990;9:407–414.PubMed

Ruchaud-Sparagano MH, Westley BR, May FE. The trefoil protein TFF1 is bound to MUC5AC in human gastric mucosa. Cell Mol Life Sci. 2004;61:1946–1954.PubMedCrossRef

Hanby AM, Poulsom R, Singh S, Elia G, Jeffery RE, Wright NA. Spasmolytic polypeptide is a major antral peptide: distribution of the trefoil peptides human spasmolytic polypeptide and pS2 in the stomach. Gastroenterology. 1993;105:1110–1116.PubMed

Thim L. Trefoil peptides: from structure to function. Cell Mol Life Sci. 1997;53:888–903.PubMedCrossRef

Sands BE, Podolsky DK. The trefoil peptide family. Annu Rev Physiol. 1996;58:253–273.PubMedCrossRef

Wong WM, Poulsom R, Wright NA. Trefoil peptides. Gut. 1999;44:890–895.PubMedCrossRef

10.

Hoffmann W. Trefoil factor family (TFF) peptides: regulators of mucosal regeneration and repair, and more. Peptides. 2004;25:727–730.PubMedCrossRef

11.

Hoffmann W. Trefoil factors TFF (trefoil factor family) peptide-triggered signals promoting mucosal restitution. Cell Mol Life Sci. 2005;62:2932–2938.PubMedCrossRef

12.

Ota H, Hayama M, Momose M, et al. Co-localization of TFF2 with gland mucous cell mucin in gastric mucous cells and in extracellular mucous gel adherent to normal and damaged gastric mucosa. Histochem Cell Biol. 2006;126:617–625.PubMedCrossRef

13.

Ichikawa T, Ota H, Sugiyama A, et al. Effects of a novel histamine H2-receptor antagonist, lafutidine, on the mucus barrier of human gastric mucosa. J Gastroenterol Hepatol. 2007;22:1800–1805.PubMedCrossRef

14.

Suzuki K, Hayama M, Nakamura M, et al. Trefoil factor 2 in gland mucous cell mucin in the mucous gel covering normal or damaged gastric mucosa using the Mongolian gerbil model. Scand J Gastroenterol. 2006;41:1390–1397.PubMedCrossRef

15.

Marshall BJ, Warren JR. Unidentified curved bacilli in the stomach of patients with gastritis and peptic ulceration. Lancet. 1984;1:1311–1315.PubMedCrossRef

16.

Peek RM Jr, Blaser MJ. Helicobacter pylori and gastrointestinal tract adenocarcinomas. Nat Rev Cancer. 2002;2:28–37.PubMedCrossRef

17.

Hidaka E, Ota H, Hidaka H, et al. Helicobacter pylori and two ultrastructurally distinct layers of gastric mucous cell mucins in the surface mucous gel layer. Gut. 2001;49:474–480.PubMedCrossRef

18.

Shimizu T, Akamatsu T, Sugiyama A, Ota H, Katsuyama T. Helicobacter pylori and the surface mucous gel layer of the human stomach. Helicobacter. 1996;1:207–218.PubMedCrossRef

19.

Kawakubo M, Ito Y, Okimura Y, et al. Natural antibiotic function of a human gastric mucin against Helicobacter pylori infection. Science. 2004;305:1003–1006.PubMedCrossRef

20.

Kubota S, Yamauchi K, Kumagai T, et al. Quantitative determination of gland mucous cells-type mucin using a monoclonal antibody, HIK1083: its pathophysiological changes in human gastric juice. Clin Chim Acta. 2007;377:261–267.PubMedCrossRef

21.

Laemmli UK. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970;227:680–685.PubMedCrossRef

22.

Asaka M, Kato M, Takahashi S, et al. Guidelines for the management of Helicobacter pylori infection in Japan: 2009 revised edition. Helicobacter. 2010;15:1–20.PubMedCrossRef

23.

Vestergaard EM, Brynskov J, Ejskjaer K, et al. Immunoassays of human trefoil factors 1 and 2: measured on serum from patients with inflammatory bowel disease. Scand J Clin Lab Invest. 2004;64:146–156.PubMedCrossRef

24.

Semple JI, Newton JL, Westley BR, May FE. Dramatic diurnal variation in the concentration of the human trefoil peptide TFF2 in gastric juice. Gut. 2001;48:648–655.PubMedCrossRef

25.

Matsuda K, Yamauchi K, Matsumoto T, Sano K, Yamaoka Y, Ota H. Quantitative analysis of the effect of Helicobacter pylori on the expressions of SOX2, CDX2, MUC2, MUC5AC, MUC6, TFF1, TFF2, and TFF3 mRNAs in human gastric carcinoma cells. Scand J Gastroenterol. 2008;43:25–33.PubMedCrossRef

26.

Van De Bovenkamp JH, Korteland-Van Male AM, Buller HA, Einerhand AW, Dekker J. Infection with Helicobacter pylori affects all major secretory cell populations in the human antrum. Dig Dis Sci. 2005;50:1078–1086.CrossRef

27.

Matsuzawa M, Ota H, Hayama M, et al. Helicobacter pylori infection up-regulates gland mucous cell-type mucins in gastric pyloric mucosa. Helicobacter. 2003;8:594–600.CrossRef

28.

Thim L, Madsen F, Poulsen SS. Effect of trefoil factors on the viscoelastic properties of mucus gels. Eur J Clin Invest. 2002;32:519–527.PubMedCrossRef

29.

Tanaka S, Podolsky DK, Engel E, Guth PH, Kaunitz JD. Human spasmolytic polypeptide decreases proton permeation through gastric mucus in vivo and in vitro. Am J Physiol. 1997;272:G1473–G1480.PubMed

30.

Playford RJ, Marchbank T, Chinery R, et al. Human spasmolytic polypeptide is a cytoprotective agent that stimulates cell migration. Gastroenterology. 1995;108:108–116.PubMedCrossRef

31.

Babyatsky MW, deBeaumont M, Thim L, Podolsky DK. Oral trefoil peptides protect against ethanol- and indomethacin-induced gastric injury in rats. Gastroenterology. 1996;110:489–497.PubMedCrossRef

32.

Hernandez C, Santamatilde E, McCreath KJ, et al. Induction of trefoil factor (TFF)1, TFF2 and TFF3 by hypoxia is mediated by hypoxia inducible factor-1: implications for gastric mucosal healing. Br J Pharmacol. 2009;156:262–272.PubMedCrossRef

33.

Bhattacharyya A, Chattopadhyay R, Hall EH, Mebrahtu ST, Ernst PB, Crowe SE. Mechanism of hypoxia-inducible factor 1 alpha-mediated Mcl1 regulation in Helicobacter pylori-infected human gastric epithelium. Am J Physiol Gastrointest Liver Physiol. 2010;299:G1177–G1186.PubMedCrossRef

34.

Rosler S, Haase T, Claassen H, et al. Trefoil factor 3 is induced during degenerative and inflammatory joint disease, activates matrix metalloproteinases, and enhances apoptosis of articular cartilage chondrocytes. Arthritis Rheum. 2010;62:815–825.PubMedCrossRef

35.

Enss ML, Cornberg M, Wagner S, et al. Proinflammatory cytokines trigger MUC gene expression and mucin release in the intestinal cancer cell line LS180. Inflamm Res. 2000;49:162–169.PubMedCrossRef

36.

Yamaoka Y, Kita M, Kodama T, Sawai N, Imanishi J. Helicobacter pylori cagA gene and expression of cytokine messenger RNA in gastric mucosa. Gastroenterology. 1996;110:1744–1752.PubMedCrossRef

Titel: Pathophysiological Investigation of the Gastric Surface Mucous Gel Layer of Patients with Helicobacter pylori Infection by Using Immunoassays for Trefoil Factor Family 2 and Gastric Gland Mucous Cell-Type Mucin in Gastric Juice
verfasst von: Seiko Kubota
Kazuyoshi Yamauchi
Mitsutoshi Sugano
Kenji Kawasaki
Atsushi Sugiyama
Kenji Matsuzawa
Taiji Akamatsu
Yasukazu Ohmoto
Hiroyoshi Ota
Publikationsdatum: 01.12.2011
Verlag: Springer US
Erschienen in: Digestive Diseases and Sciences / Ausgabe 12/2011
Print ISSN: 0163-2116
Elektronische ISSN: 1573-2568
DOI: https://doi.org/10.1007/s10620-011-1724-9

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

^{Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag}

Kostenlos registrieren

Neu im Fachgebiet Innere Medizin

„Jeder Fall von plötzlichem Tod muss obduziert werden!“

17.05.2024 Plötzlicher Herztod Nachrichten

Ein signifikanter Anteil der Fälle von plötzlichem Herztod ist genetisch bedingt. Um ihre Verwandten vor diesem Schicksal zu bewahren, sollten jüngere Personen, die plötzlich unerwartet versterben, ausnahmslos einer Autopsie unterzogen werden.

Hirnblutung unter DOAK und VKA ähnlich bedrohlich

17.05.2024 Direkte orale Antikoagulanzien Nachrichten

Kommt es zu einer nichttraumatischen Hirnblutung, spielt es keine große Rolle, ob die Betroffenen zuvor direkt wirksame orale Antikoagulanzien oder Marcumar bekommen haben: Die Prognose ist ähnlich schlecht.

Schlechtere Vorhofflimmern-Prognose bei kleinem linken Ventrikel

17.05.2024 Vorhofflimmern Nachrichten

Nicht nur ein vergrößerter, sondern auch ein kleiner linker Ventrikel ist bei Vorhofflimmern mit einer erhöhten Komplikationsrate assoziiert. Der Zusammenhang besteht nach Daten aus China unabhängig von anderen Risikofaktoren.

Semaglutid bei Herzinsuffizienz: Wie erklärt sich die Wirksamkeit?

17.05.2024 Herzinsuffizienz Nachrichten

Bei adipösen Patienten mit Herzinsuffizienz des HFpEF-Phänotyps ist Semaglutid von symptomatischem Nutzen. Resultiert dieser Benefit allein aus der Gewichtsreduktion oder auch aus spezifischen Effekten auf die Herzinsuffizienz-Pathogenese? Eine neue Analyse gibt Aufschluss.

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

Newsletter bestellen

Die Highlights vom Kongress des American College of Cardiology 2024

Springer Medizin

Abstract

Background

Aims

Methods

Results

Conclusions

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 12/2011

Serum sTREM-1 as a Surrogate Marker of Treatment Outcome in Patients with Peptic Ulcer Disease

Mechanical Characteristics of Distension-Evoked Peristaltic Contractions in the Esophagus of Systemic Sclerosis Patients

Cameron Ulcers: You Will Find Only What You Seek

Predicting the Severity of Acute Pancreatitis: Choose the Right Horse Before Hitching the Cart

Montelukast Was Inefficient in Maintaining Steroid-Induced Remission in Adult Eosinophilic Esophagitis