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

Rossi O, Karczewski J, Stolte EH, Brummer RJ, van Nieuwenhoven MA, Meijerink M, van Neerven JR, van Ijzendoorn SC, van Baarlen P, Wells JM - BMC Res Notes (2013)

Bottom Line: In the intestinal mucosa, several adaptations of TLR signalling have evolved to avoid chronic inflammatory responses to the presence of commensal microbes.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.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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Host-Microbe Interactomics Group, ASG, University of Wageningen, Wageningen, The Netherlands. jerry.wells@wur.nl.

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.

Show MeSH

Related in: MedlinePlus

In human duodenal and colonic tissues, CXCR1 is expressed on the apical surface of villus enterocytes and is absent in the crypts. Duodenum and colon biopsies stained with anti-occludin (red), DRAQ5 (blue) and anti-CXCR1 (green). In villus enterocytes, CXCR1 is located on the apical membrane (sections of duodenum (a) and colon (c)), and surrounding the nuclei of cells in the lamina propria (a, arrow). CXCR1 is absent in the enterocytes lining the crypts of duodenum (b) and colon (d).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4231470&req=5

Figure 3: In human duodenal and colonic tissues, CXCR1 is expressed on the apical surface of villus enterocytes and is absent in the crypts. Duodenum and colon biopsies stained with anti-occludin (red), DRAQ5 (blue) and anti-CXCR1 (green). In villus enterocytes, CXCR1 is located on the apical membrane (sections of duodenum (a) and colon (c)), and surrounding the nuclei of cells in the lamina propria (a, arrow). CXCR1 is absent in the enterocytes lining the crypts of duodenum (b) and colon (d).

Mentions: The absorptive enterocytes forming the epithelium and the enterocytes lining the crypts, were revealed by staining for the TJ protein occludin (red) and nuclear DNA (blue, Figure 3a-d). In the duodenum, CXCR1 was detected on the apical membrane of villus epithelial cells and not in crypt epithelium (green, Figure 3a and b). Similarly, in human colonic tissue CXCR1 was detected on the top of the epithelium and not in crypt enterocytes (green, Figure 3c and d). The surface of immune cells present in the lamina propria in colonic and duodenal tissues also stained positive for CXCR1 (Figure 3a and c).


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

Rossi O, Karczewski J, Stolte EH, Brummer RJ, van Nieuwenhoven MA, Meijerink M, van Neerven JR, van Ijzendoorn SC, van Baarlen P, Wells JM - BMC Res Notes (2013)

In human duodenal and colonic tissues, CXCR1 is expressed on the apical surface of villus enterocytes and is absent in the crypts. Duodenum and colon biopsies stained with anti-occludin (red), DRAQ5 (blue) and anti-CXCR1 (green). In villus enterocytes, CXCR1 is located on the apical membrane (sections of duodenum (a) and colon (c)), and surrounding the nuclei of cells in the lamina propria (a, arrow). CXCR1 is absent in the enterocytes lining the crypts of duodenum (b) and colon (d).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4231470&req=5

Figure 3: In human duodenal and colonic tissues, CXCR1 is expressed on the apical surface of villus enterocytes and is absent in the crypts. Duodenum and colon biopsies stained with anti-occludin (red), DRAQ5 (blue) and anti-CXCR1 (green). In villus enterocytes, CXCR1 is located on the apical membrane (sections of duodenum (a) and colon (c)), and surrounding the nuclei of cells in the lamina propria (a, arrow). CXCR1 is absent in the enterocytes lining the crypts of duodenum (b) and colon (d).
Mentions: The absorptive enterocytes forming the epithelium and the enterocytes lining the crypts, were revealed by staining for the TJ protein occludin (red) and nuclear DNA (blue, Figure 3a-d). In the duodenum, CXCR1 was detected on the apical membrane of villus epithelial cells and not in crypt epithelium (green, Figure 3a and b). Similarly, in human colonic tissue CXCR1 was detected on the top of the epithelium and not in crypt enterocytes (green, Figure 3c and d). The surface of immune cells present in the lamina propria in colonic and duodenal tissues also stained positive for CXCR1 (Figure 3a and c).

Bottom Line: In the intestinal mucosa, several adaptations of TLR signalling have evolved to avoid chronic inflammatory responses to the presence of commensal microbes.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.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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Host-Microbe Interactomics Group, ASG, University of Wageningen, Wageningen, The Netherlands. jerry.wells@wur.nl.

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.

Show MeSH
Related in: MedlinePlus