Skip to main content
SpringerLink
Log in

Decreased mucosal expression of intestinal alkaline phosphatase in children with coeliac disease

  • Original Article
  • Published:
Virchows Archiv Aims and scope Submit manuscript

Abstract

A major function of the enzyme intestinal alkaline phosphatase (iAP) is the detoxification of lipopolysaccharide (LPS), the ligand of Toll-like receptor 4 (TLR4). Hence, iAP has a role in the defence of maintaining intestinal barrier integrity. As intestinal barrier integrity is impaired in coeliac disease (CD), we tested the expression and localization of iAP in duodenal mucosa specimens from children with newly diagnosed CD (n = 10), with CD on gluten-free diet (GFD) (n = 5) and compared to those from ten healthy children. The mRNA and protein expression was determined by RT-PCR and Western blot analysis, respectively. Tissue localization of iAP and TLR4 was determined by immunofluorescence staining. iAP protein expression level was significantly lower than normal in newly diagnosed CD, while it was normalised in children on GFD. iAP and TLR4 colocalized at the epithelial surface of duodenal mucosa in each group of subjects enrolled. The finding of decreased iAP protein levels in newly diagnosed CD is consistent with its role in decreased intestinal barrier integrity. The latter may be the result of decreased LPS-detoxifying ability.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Maynard CL, Weaver CT (2011) Immunology: context is key in the gut. Nature 471:169–170

    Article  PubMed  CAS  Google Scholar 

  2. Dickson BC, Streutker CJ, Chetty R (2006) Coeliac disease: an update for pathologists. J Clin Pathol 59:1008–1016

    Article  PubMed  CAS  Google Scholar 

  3. Ensari A (2010) Gluten-sensitive enteropathy (celiac disease): controversies in diagnosis and classification. Arch Pathol Lab Med 134:826–836

    PubMed  Google Scholar 

  4. Cario E (2008) Barrier-protective function of intestinal epithelial Toll-like receptor 2. Mucosal Immunol 1(Suppl 1):S62–S66

    Article  PubMed  CAS  Google Scholar 

  5. Abreu M, Fukata M, Arditi M (2005) TLR signaling in the gut in health and disease. J Immunol 174:4453–4460

    PubMed  CAS  Google Scholar 

  6. Triantafilou M, Triantafilou K (2002) Lipopolysaccharide recognition: CD14, TLRs and the LPS-activation cluster. Trends Immunol 23:301–304

    Article  PubMed  CAS  Google Scholar 

  7. Baumgart D, Thomas S, Przesdzing I, Metzke D, Bielecki C, Lehmann S, Lehnardt S, Dörffel Y, Sturm A, Scheffold A, Schmitz J, Radbruch A (2009) Exaggerated inflammatory response of primary human myeloid dendritic cells to lipopolysaccharide in patients with inflammatory bowel disease. Clin Exp Immunol 157:423–436

    Article  PubMed  CAS  Google Scholar 

  8. Szebeni B, Veres G, Dezsofi A, Rusai K, Vannay A, Bokodi G, Vásárhelyi B, Korponay-Szabó I, Tulassay T, Arató A (2007) Increased mucosal expression of Toll-like receptor (TLR)2 and TLR4 in coeliac disease. J Pediatr Gastroenterol Nutr 45:187–193

    Article  PubMed  CAS  Google Scholar 

  9. Cseh Á, Vásárhelyi B, Szalay B, Molnár K, Nagy-Szakál D, Treszl A, Vannay Á, Arató A, Tulassay T, Veres G (2011) Immune phenotype of children with newly diagnosed and gluten-free diet-treated celiac disease. Dig Dis Sci 56:792–798

    Article  PubMed  CAS  Google Scholar 

  10. Lallès JP (2010) Intestinal alkaline phosphatase: multiple biological roles in maintenance of intestinal homeostasis and modulation by diet. Nutr Rev 68:323–332

    Article  PubMed  Google Scholar 

  11. Bates J, Akerlund J, Mittge E, Guillemin K (2007) Intestinal alkaline phosphatase detoxifies lipopolysaccharide and prevents inflammation in zebrafish in response to the gut microbiota. Cell Host Microbe 2:371–382

    Article  PubMed  CAS  Google Scholar 

  12. Goldberg RF, Austen WG, Zhang X, Munene G, Mostafa G, Biswas S, McCormack M, Eberlin KR, Nguyen JT, Tatlidede HS, Warren HS, Narisawa S, Millán JL, Hodin RA (2008) Intestinal alkaline phosphatase is a gut mucosal defense factor maintained by enteral nutrition. Proc Natl Acad Sci U S A 105:3551–3556

    Article  PubMed  CAS  Google Scholar 

  13. Geddes K, Philpott D (2008) A new role for intestinal alkaline phosphatase in gut barrier maintenance. Gastroenterology 135:8–12

    Article  PubMed  CAS  Google Scholar 

  14. Tuin A, Poelstra K, de Jager-Krikken A, Bok L, Raaben W, Velders M, Dijkstra G (2009) Role of alkaline phosphatase in colitis in man and rats. Gut 58:379–387

    Article  PubMed  CAS  Google Scholar 

  15. Lukas M, Drastich P, Konecny M, Gionchetti P, Urban O, Cantoni F, Bortlik M, Duricova D, Bulitta M (2010) Exogenous alkaline phosphatase for the treatment of patients with moderate to severe ulcerative colitis. Inflamm Bowel Dis 16:1180–1186

    PubMed  Google Scholar 

  16. Prasad K, Thapa B, Nain C, Sharma A, Singh K (2008) Brush border enzyme activities in relation to histological lesion in pediatric celiac disease. J Gastroenterol Hepatol 23:e348–e352

    Article  PubMed  CAS  Google Scholar 

  17. Ribes-Koninckx C, Mearin M, Korponay-Szabó I, Shamir R, Husby S, Ventura A, Branski D, Catassi C, Koletzko S, Mäki M, Troncone R, Zimmer K, The ESPGHAN Working Group on Coeliac Disease Diagnosis (2012) Coeliac disease diagnosis: espghan 1990 Criteria or need for a change? Results of a questionnaire. J Pediatr Gastroenterol Nutr 54(1):15–19

    Article  PubMed  CAS  Google Scholar 

  18. Meijer JW, Wahab PJ, Mulder CJ (2003) Small intestinal biopsies in celiac disease: duodenal or jejunal? Virchows Arch 442:124–128

    PubMed  Google Scholar 

  19. Dalgic B, Sari S, Basturk B, Ensari A, Egritas O, Bukulmez A, Baris Z, TurkishCeliac Study Group (2011) Prevalence of celiac disease in healthy Turkish school children. Am J Gastroenterol 106:1512–1517

    Article  PubMed  CAS  Google Scholar 

  20. Gorgun J, Portyanko A, Marakhouski Y, Cherstvoy E (2009) Tissue transglutaminase expression in celiac mucosa: an immunohistochemical study. Virchows Arch 455:363–373

    Article  PubMed  CAS  Google Scholar 

  21. Wahab PJ, Meijer JW, Mulder CJ (2002) Histologic follow-up of people with celiac disease on a gluten-free diet: slow and incomplete recovery. Am J Clin Pathol 118:459–463

    Article  PubMed  Google Scholar 

  22. Szakál DN, Gyorffy H, Arató A, Cseh A, Molnár K, Papp M, Dezsofi A, Veres G (2010) Mucosal expression of claudins 2, 3 and 4 in proximal and distal part of duodenum in children with coeliac disease. Virchows Arch 456:245–250

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

We thank Mária Bernáth for her excellent technical assistance. This work was supported by grants OTKA-76316, OTKA-K81117, TÁMOP 4.2.2. B-10/1-2010-2013, and ETT-028-02. Gábor Veres and Ádam Vannay are holders of the János Bolyai Research grant; this article was supported by the János Bolyai Research Scholarship of the Hungarian Academy of Sciences.

Conflict of interest

We declare that we have no conflict of interest.

Author information

Authors and Affiliations

  1. 1st Department of Paediatrics, Semmelweis University, Bókay u. 53, H-1083, Budapest, Hungary

    Kriszta Molnár, András Arató, Antal Dezsőfi & Gabor Veres

  2. Research Group for Paediatrics and Nephrology, Semmelweis University and Hungarian Academy of Sciences, Budapest, Hungary

    Ádám Vannay & Erna Sziksz

  3. SE-MTA “Lendulet” Diabetes Research Group, Budapest, Hungary

    Nóra Fanni Bánki

  4. 2nd Department of Pathology, Semmelweis University, Budapest, Hungary

    Hajnalka Győrffy

Authors
  1. Kriszta Molnár
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ádám Vannay
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Erna Sziksz
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Nóra Fanni Bánki
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Hajnalka Győrffy
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. András Arató
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Antal Dezsőfi
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Gabor Veres
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Gabor Veres.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Molnár, K., Vannay, Á., Sziksz, E. et al. Decreased mucosal expression of intestinal alkaline phosphatase in children with coeliac disease. Virchows Arch 460, 157–161 (2012). https://doi.org/10.1007/s00428-011-1188-5

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00428-011-1188-5

Keywords

Search

Navigation