Vectorial secretion of interleukin-8 mediates autocrine signalling in intestinal epithelial cells via apically located CXCR1

O. Rossi, J. Karczewski, E.H. Stolte, R.J. Brummer, M.A. van Nieuwenhoven, M. Meijerink, R.J.J. van Neerven, S.C. van Ijzendoorn, P. van Baarlen, J. Wells

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Abstract

Background

In the intestinal mucosa, several adaptations of TLR signalling have evolved to avoid chronic inflammatory responses to the presence of commensal microbes. Here we investigated whether polarized monolayers of intestinal epithelial cells might regulate inflammatory responses by secreting IL-8 in a vectorial fashion (i.e. apical versus basolateral) depending on the location of the TLR stimulus.

Results

In the Caco-2 BBE model of polarized villus-like epithelium, apical stimulation with TLR2 and TLR5 ligands resulted in the apical secretion of IL-8. The CXCR1 receptor for IL-8 was expressed only on the apical membrane of Caco-2 BBE cells and differentiated epithelial cells in the human small intestine and colon. Transcriptome analyses revealed that Caco-2 BBE cells respond to stimulation with IL-8 supporting the hypothesis that IL-8 induces G protein-coupled receptor signalling.

Conclusions

These results show that IL-8 induces autocrine signalling via an apical CXCR1 in Caco-2 BBE intestinal epithelial cells and that this receptor is also expressed on the apical surface of differentiated human intestinal epithelial cells in vivo, suggesting an autocrine function for IL-8 secreted in the lumen.
LanguageEnglish
Article number431
JournalBMC Research Notes
Volume6
Issue number1
DOIs
Publication statusPublished - 2013

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Autocrine Communication
Interleukin-8
Epithelial Cells
Caco-2 Cells
Interleukin-8A Receptors
Gene Expression Profiling
Intestinal Mucosa
G-Protein-Coupled Receptors
Small Intestine
Monolayers
Colon
Epithelium
Ligands
Membranes

Cite this

Rossi, O. ; Karczewski, J. ; Stolte, E.H. ; Brummer, R.J. ; van Nieuwenhoven, M.A. ; Meijerink, M. ; van Neerven, R.J.J. ; van Ijzendoorn, S.C. ; van Baarlen, P. ; Wells, J. / Vectorial secretion of interleukin-8 mediates autocrine signalling in intestinal epithelial cells via apically located CXCR1. In: BMC Research Notes. 2013 ; Vol. 6, No. 1.
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title = "Vectorial secretion of interleukin-8 mediates autocrine signalling in intestinal epithelial cells via apically located CXCR1",
abstract = "BackgroundIn the intestinal mucosa, several adaptations of TLR signalling have evolved to avoid chronic inflammatory responses to the presence of commensal microbes. Here we investigated whether polarized monolayers of intestinal epithelial cells might regulate inflammatory responses by secreting IL-8 in a vectorial fashion (i.e. apical versus basolateral) depending on the location of the TLR stimulus.ResultsIn the Caco-2 BBE model of polarized villus-like epithelium, apical stimulation with TLR2 and TLR5 ligands resulted in the apical secretion of IL-8. The CXCR1 receptor for IL-8 was expressed only on the apical membrane of Caco-2 BBE cells and differentiated epithelial cells in the human small intestine and colon. Transcriptome analyses revealed that Caco-2 BBE cells respond to stimulation with IL-8 supporting the hypothesis that IL-8 induces G protein-coupled receptor signalling.ConclusionsThese results show that IL-8 induces autocrine signalling via an apical CXCR1 in Caco-2 BBE intestinal epithelial cells and that this receptor is also expressed on the apical surface of differentiated human intestinal epithelial cells in vivo, suggesting an autocrine function for IL-8 secreted in the lumen.",
author = "O. Rossi and J. Karczewski and E.H. Stolte and R.J. Brummer and {van Nieuwenhoven}, M.A. and M. Meijerink and {van Neerven}, R.J.J. and {van Ijzendoorn}, S.C. and {van Baarlen}, P. and J. Wells",
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Vectorial secretion of interleukin-8 mediates autocrine signalling in intestinal epithelial cells via apically located CXCR1. / Rossi, O.; Karczewski, J.; Stolte, E.H.; Brummer, R.J.; van Nieuwenhoven, M.A.; Meijerink, M.; van Neerven, R.J.J.; van Ijzendoorn, S.C.; van Baarlen, P.; Wells, J.

In: BMC Research Notes, Vol. 6, No. 1, 431, 2013.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Vectorial secretion of interleukin-8 mediates autocrine signalling in intestinal epithelial cells via apically located CXCR1

AU - Rossi, O.

AU - Karczewski, J.

AU - Stolte, E.H.

AU - Brummer, R.J.

AU - van Nieuwenhoven, M.A.

AU - Meijerink, M.

AU - van Neerven, R.J.J.

AU - van Ijzendoorn, S.C.

AU - van Baarlen, P.

AU - Wells, J.

PY - 2013

Y1 - 2013

N2 - BackgroundIn the intestinal mucosa, several adaptations of TLR signalling have evolved to avoid chronic inflammatory responses to the presence of commensal microbes. Here we investigated whether polarized monolayers of intestinal epithelial cells might regulate inflammatory responses by secreting IL-8 in a vectorial fashion (i.e. apical versus basolateral) depending on the location of the TLR stimulus.ResultsIn the Caco-2 BBE model of polarized villus-like epithelium, apical stimulation with TLR2 and TLR5 ligands resulted in the apical secretion of IL-8. The CXCR1 receptor for IL-8 was expressed only on the apical membrane of Caco-2 BBE cells and differentiated epithelial cells in the human small intestine and colon. Transcriptome analyses revealed that Caco-2 BBE cells respond to stimulation with IL-8 supporting the hypothesis that IL-8 induces G protein-coupled receptor signalling.ConclusionsThese results show that IL-8 induces autocrine signalling via an apical CXCR1 in Caco-2 BBE intestinal epithelial cells and that this receptor is also expressed on the apical surface of differentiated human intestinal epithelial cells in vivo, suggesting an autocrine function for IL-8 secreted in the lumen.

AB - BackgroundIn the intestinal mucosa, several adaptations of TLR signalling have evolved to avoid chronic inflammatory responses to the presence of commensal microbes. Here we investigated whether polarized monolayers of intestinal epithelial cells might regulate inflammatory responses by secreting IL-8 in a vectorial fashion (i.e. apical versus basolateral) depending on the location of the TLR stimulus.ResultsIn the Caco-2 BBE model of polarized villus-like epithelium, apical stimulation with TLR2 and TLR5 ligands resulted in the apical secretion of IL-8. The CXCR1 receptor for IL-8 was expressed only on the apical membrane of Caco-2 BBE cells and differentiated epithelial cells in the human small intestine and colon. Transcriptome analyses revealed that Caco-2 BBE cells respond to stimulation with IL-8 supporting the hypothesis that IL-8 induces G protein-coupled receptor signalling.ConclusionsThese results show that IL-8 induces autocrine signalling via an apical CXCR1 in Caco-2 BBE intestinal epithelial cells and that this receptor is also expressed on the apical surface of differentiated human intestinal epithelial cells in vivo, suggesting an autocrine function for IL-8 secreted in the lumen.

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