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Expression of Toll-Like Receptors in Enterocromaffin-Like Cells and Their Function in Histamine Release

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Abstract

Introduction

Enterocromaffin-like cells (ECL) are specialized endocrine gastric cells able to release histamine, which in turn controls gastric acid production by parietal cells. Helicobacter pylori infection and other conditions signal in the gastrointestinal tract via Toll-like receptors (TLRs) and modify gastric acid production, but there is no evidence of expression and function of TLRs in ECL cells. In this work, we analyzed gene and protein expression of TLR-2, 4, 5, and 9, and other molecules involved in TLR signaling in ECL cells.

Material and Methods

ECL cells were isolated from Sprague–Dawley rats. The histamine-releasing ability of TLR ligands was also evaluated after culture of the ECL cells for a short time.

Results

With ECL cells that expressed the TLR-2, TLR-4, TLR-5, and TLR-9 genes we were able to confirm protein expression for TLR-2, TLR-5, and TLR-9. Functionally, ECL cells were able to release histamine in response to TLR-2 stimulation by peptidoglycan (PGN), a TLR-2 ligand. After PGN stimulus, IRAK and p38 phosphorylation could be observed. SB 203580, a p38 inhibitor, reversed PGN-induced histamine release. Lipopolysaccharide (LPS), a TLR-4 ligand, was also able to induce histamine release in ECL cells, but by a mechanism independent of TLRs.

Conclusions

We have demonstrated for the first time that ECL cells express TLRs and respond to TLR-2 ligand by increasing histamine release. This response could be involved in host defense against gastrointestinal bacterial pathogens but could also contribute to control of gastric acid secretion in the absence of pathogens.

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Acknowledgments

This research Project is supported by Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP).

Conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Clinical Pharmacology and Gastroenterology Unit, São Francisco University Medical School, Av. São Francisco de Assis 218, Bragança Paulista, SP, 12916-900, Brazil

    Carolina Bernardi Stefani, Rafael Martins de Oliveira, Angélica Aparecida Antoniellis Silveira, Lucio Fabio Caldas Ferraz, Marcelo Lima Ribeiro, Alessandra Gambero & José Pedrazzoli Júnior

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  1. Carolina Bernardi Stefani
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  2. Rafael Martins de Oliveira
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  3. Angélica Aparecida Antoniellis Silveira
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  4. Lucio Fabio Caldas Ferraz
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  5. Marcelo Lima Ribeiro
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  6. Alessandra Gambero
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  7. José Pedrazzoli Júnior
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Correspondence to Alessandra Gambero.

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Stefani, C.B., de Oliveira, R.M., Silveira, A.A.A. et al. Expression of Toll-Like Receptors in Enterocromaffin-Like Cells and Their Function in Histamine Release. Dig Dis Sci 57, 2270–2277 (2012). https://doi.org/10.1007/s10620-012-2176-6

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  • DOI: https://doi.org/10.1007/s10620-012-2176-6

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