Toll-like receptor 2 signalling and the lysosomal machinery in Barrett’s esophagus

Romy E. Verbeek, Peter D. Siersema, Frank P. Vleggaar, Fiebo J. ten Kate, George Posthuma, Rhonda F. Souza, Judith de Haan, Jantine W P M van Baal

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Background & Aims: Inflammation plays an important role in the development of esophageal adenocarcinoma and its metaplastic precursor lesion, Barrett’s esophagus. Toll-like receptor (TLR) 2 signalling and lysosomal function have been linked to inflammation-associated carcinogenesis. We examined the expression of TLR2 in the esophagus and the effect of long-term TLR2 activation on morphological changes and expression of factors involved in lysosomal function in a Barrett’s esophagus epithelium cell line. Methods: TLR2 expression in normal squamous esophagus, reflux esophagitis, Barrett’s esophagus and esophageal adenocarcinoma biopsies was assessed with Q-RT-PCR, in situ hybridization and immunohistochemistry. Barrett’s esophagus epithelium cells (BAR-T) were incubated with acid and bile salts in the presence or absence of the TLR2 agonist Pam3CSK4 for a period up to 4 weeks. Morphological changes were assessed with electron microscopy, while Q-RT-PCR was used to determine the expression of lysosomal enzymes (Cathepsin B and C) and factors involved in endocytosis (LAMP-1 and M6PR) and autophagy (LC3 and Rab7). Results: TLR2 was expressed in normal squamous esophagus, reflux esophagitis, Barrett’s esophagus but was most prominent in esophageal adenocarcinoma. Long-term TLR2 activation in acid and bile salts exposed BAR-T cells resulted in more and larger lysosomes, more mitochondria and increased expression of LAMP-1, M6PR, Cathepsin B and C when compared to BAR-T cells incubated with acid and bile salts but no TLR2 agonist. Factors associated with autophagy (LC3 and Rab7) expression remained largely unchanged. Conclusion: Activation of TLR2 in acid and bile salts exposed Barrett epithelium cells resulted in an increased number of mitochondria and lysosomes and increased expression of lysosomal enzymes and factors involved in endocytosis.

Original languageEnglish (US)
Pages (from-to)273-282
Number of pages10
JournalJournal of Gastrointestinal and Liver Diseases
Volume25
Issue number3
StatePublished - Sep 1 2016

Fingerprint

Toll-Like Receptor 2
Barrett Esophagus
Bile Acids and Salts
Cathepsin C
Esophagus
Cathepsin B
Peptic Esophagitis
Adenocarcinoma
Autophagy
Endocytosis
Lysosomes
Mitochondria
Inflammation
T-Lymphocytes
Polymerase Chain Reaction
Enzymes
In Situ Hybridization
Electron Microscopy
Carcinogenesis
Immunohistochemistry

Keywords

  • Barrett’s esophagus
  • Esophageal adenocarcinoma
  • Lysosomes
  • Toll-like receptor 2

ASJC Scopus subject areas

  • Gastroenterology

Cite this

Verbeek, R. E., Siersema, P. D., Vleggaar, F. P., ten Kate, F. J., Posthuma, G., Souza, R. F., ... van Baal, J. W. P. M. (2016). Toll-like receptor 2 signalling and the lysosomal machinery in Barrett’s esophagus. Journal of Gastrointestinal and Liver Diseases, 25(3), 273-282.

Toll-like receptor 2 signalling and the lysosomal machinery in Barrett’s esophagus. / Verbeek, Romy E.; Siersema, Peter D.; Vleggaar, Frank P.; ten Kate, Fiebo J.; Posthuma, George; Souza, Rhonda F.; de Haan, Judith; van Baal, Jantine W P M.

In: Journal of Gastrointestinal and Liver Diseases, Vol. 25, No. 3, 01.09.2016, p. 273-282.

Research output: Contribution to journalArticle

Verbeek, RE, Siersema, PD, Vleggaar, FP, ten Kate, FJ, Posthuma, G, Souza, RF, de Haan, J & van Baal, JWPM 2016, 'Toll-like receptor 2 signalling and the lysosomal machinery in Barrett’s esophagus', Journal of Gastrointestinal and Liver Diseases, vol. 25, no. 3, pp. 273-282.
Verbeek RE, Siersema PD, Vleggaar FP, ten Kate FJ, Posthuma G, Souza RF et al. Toll-like receptor 2 signalling and the lysosomal machinery in Barrett’s esophagus. Journal of Gastrointestinal and Liver Diseases. 2016 Sep 1;25(3):273-282.
Verbeek, Romy E. ; Siersema, Peter D. ; Vleggaar, Frank P. ; ten Kate, Fiebo J. ; Posthuma, George ; Souza, Rhonda F. ; de Haan, Judith ; van Baal, Jantine W P M. / Toll-like receptor 2 signalling and the lysosomal machinery in Barrett’s esophagus. In: Journal of Gastrointestinal and Liver Diseases. 2016 ; Vol. 25, No. 3. pp. 273-282.
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abstract = "Background & Aims: Inflammation plays an important role in the development of esophageal adenocarcinoma and its metaplastic precursor lesion, Barrett’s esophagus. Toll-like receptor (TLR) 2 signalling and lysosomal function have been linked to inflammation-associated carcinogenesis. We examined the expression of TLR2 in the esophagus and the effect of long-term TLR2 activation on morphological changes and expression of factors involved in lysosomal function in a Barrett’s esophagus epithelium cell line. Methods: TLR2 expression in normal squamous esophagus, reflux esophagitis, Barrett’s esophagus and esophageal adenocarcinoma biopsies was assessed with Q-RT-PCR, in situ hybridization and immunohistochemistry. Barrett’s esophagus epithelium cells (BAR-T) were incubated with acid and bile salts in the presence or absence of the TLR2 agonist Pam3CSK4 for a period up to 4 weeks. Morphological changes were assessed with electron microscopy, while Q-RT-PCR was used to determine the expression of lysosomal enzymes (Cathepsin B and C) and factors involved in endocytosis (LAMP-1 and M6PR) and autophagy (LC3 and Rab7). Results: TLR2 was expressed in normal squamous esophagus, reflux esophagitis, Barrett’s esophagus but was most prominent in esophageal adenocarcinoma. Long-term TLR2 activation in acid and bile salts exposed BAR-T cells resulted in more and larger lysosomes, more mitochondria and increased expression of LAMP-1, M6PR, Cathepsin B and C when compared to BAR-T cells incubated with acid and bile salts but no TLR2 agonist. Factors associated with autophagy (LC3 and Rab7) expression remained largely unchanged. Conclusion: Activation of TLR2 in acid and bile salts exposed Barrett epithelium cells resulted in an increased number of mitochondria and lysosomes and increased expression of lysosomal enzymes and factors involved in endocytosis.",
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AU - ten Kate, Fiebo J.

AU - Posthuma, George

AU - Souza, Rhonda F.

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