Resident human lamina propria immune cells serve as powerful effectors in host defense. Molecular events associated with the initiation of an intestinal inflammatory response in these cells are largely unknown. Here, we aimed to characterize phenotypic and functional changes induced in these cells at the onset of intestinal inflammation using a human intestinal organ culture model. In this model, healthy human colonic mucosa was depleted of epithelial cells by EDTA treatment. Following loss of the epithelial layer, expression of the inflammatory mediators IL1B, IL6, IL8, IL23A, TNFA, CXCL2, and the surface receptors CD14, TLR2, CD86, CD54 was rapidly induced in resident lamina propria cells in situ as determined by qRT-PCR and immunohistology. Gene microarray analysis of lamina propria cells obtained by laser-capture microdissection provided an overview of global changes in gene expression occurring during the initiation of an intestinal inflammatory response in these cells. Bioinformatic analysis gave insight into signalling pathways mediating this inflammatory response. Furthermore, comparison with published microarray datasets of inflamed mucosa in vivo (ulcerative colitis) revealed a significant overlap of differentially regulated genes underlining the in vivo relevance of the organ culture model. Furthermore, genes never been previously associated with intestinal inflammation were identified using this model. The organ culture model characterized may be useful to study molecular mechanisms underlying the initiation of an intestinal inflammatory response in normal mucosa as well as potential alterations of this response in inflammatory bowel disease.
%0 Journal Article
%1 Schroeder-Braunstein2014
%A Schröder-Braunstein, Jutta
%A Gras, Judith
%A Brors, Benedikt
%A Schwarz, Sonja
%A Szikszai, Timea
%A Lasitschka, Felix
%A Wabnitz, Guido
%A Heidtmann, Antje
%A Lee, Young-Seon
%A Schiessling, Serin
%A Leowardi, Christine
%A Al-Saeedi, Mohammed
%A Ulrich, Alexis
%A Engelke, Antonia
%A Winter, Johannes
%A Samstag, Yvonne
%A Giese, Thomas
%A Meuer, Stefan
%D 2014
%J PLoS One
%K ABI-DKFZ
%N 5
%P e97780
%R 10.1371/journal.pone.0097780
%T Initiation of an inflammatory response in resident intestinal lamina propria cells -use of a human organ culture model.
%U http://dx.doi.org/10.1371/journal.pone.0097780
%V 9
%X Resident human lamina propria immune cells serve as powerful effectors in host defense. Molecular events associated with the initiation of an intestinal inflammatory response in these cells are largely unknown. Here, we aimed to characterize phenotypic and functional changes induced in these cells at the onset of intestinal inflammation using a human intestinal organ culture model. In this model, healthy human colonic mucosa was depleted of epithelial cells by EDTA treatment. Following loss of the epithelial layer, expression of the inflammatory mediators IL1B, IL6, IL8, IL23A, TNFA, CXCL2, and the surface receptors CD14, TLR2, CD86, CD54 was rapidly induced in resident lamina propria cells in situ as determined by qRT-PCR and immunohistology. Gene microarray analysis of lamina propria cells obtained by laser-capture microdissection provided an overview of global changes in gene expression occurring during the initiation of an intestinal inflammatory response in these cells. Bioinformatic analysis gave insight into signalling pathways mediating this inflammatory response. Furthermore, comparison with published microarray datasets of inflamed mucosa in vivo (ulcerative colitis) revealed a significant overlap of differentially regulated genes underlining the in vivo relevance of the organ culture model. Furthermore, genes never been previously associated with intestinal inflammation were identified using this model. The organ culture model characterized may be useful to study molecular mechanisms underlying the initiation of an intestinal inflammatory response in normal mucosa as well as potential alterations of this response in inflammatory bowel disease.
@article{Schroeder-Braunstein2014,
__markedentry = {[bbrors:6]},
abstract = {Resident human lamina propria immune cells serve as powerful effectors in host defense. Molecular events associated with the initiation of an intestinal inflammatory response in these cells are largely unknown. Here, we aimed to characterize phenotypic and functional changes induced in these cells at the onset of intestinal inflammation using a human intestinal organ culture model. In this model, healthy human colonic mucosa was depleted of epithelial cells by EDTA treatment. Following loss of the epithelial layer, expression of the inflammatory mediators IL1B, IL6, IL8, IL23A, TNFA, CXCL2, and the surface receptors CD14, TLR2, CD86, CD54 was rapidly induced in resident lamina propria cells in situ as determined by qRT-PCR and immunohistology. Gene microarray analysis of lamina propria cells obtained by laser-capture microdissection provided an overview of global changes in gene expression occurring during the initiation of an intestinal inflammatory response in these cells. Bioinformatic analysis gave insight into signalling pathways mediating this inflammatory response. Furthermore, comparison with published microarray datasets of inflamed mucosa in vivo (ulcerative colitis) revealed a significant overlap of differentially regulated genes underlining the in vivo relevance of the organ culture model. Furthermore, genes never been previously associated with intestinal inflammation were identified using this model. The organ culture model characterized may be useful to study molecular mechanisms underlying the initiation of an intestinal inflammatory response in normal mucosa as well as potential alterations of this response in inflammatory bowel disease.},
added-at = {2015-06-29T14:32:37.000+0200},
author = {Schr{\"{o}}der-Braunstein, Jutta and Gras, Judith and Brors, Benedikt and Schwarz, Sonja and Szikszai, Timea and Lasitschka, Felix and Wabnitz, Guido and Heidtmann, Antje and Lee, Young-Seon and Schiessling, Serin and Leowardi, Christine and Al-Saeedi, Mohammed and Ulrich, Alexis and Engelke, Antonia and Winter, Johannes and Samstag, Yvonne and Giese, Thomas and Meuer, Stefan},
biburl = {https://www.bibsonomy.org/bibtex/2d885d7f585b7970b59cfa5395457fe1e/juraeva},
doi = {10.1371/journal.pone.0097780},
institution = {Institute of Immunology, University Hospital Heidelberg, Heidelberg, Germany.},
interhash = {1a070ff5ccc57bf6a692037cb649c8a4},
intrahash = {d885d7f585b7970b59cfa5395457fe1e},
journal = {PLoS One},
keywords = {ABI-DKFZ},
language = {eng},
medline-pst = {epublish},
number = 5,
owner = {bbrors},
pages = {e97780},
pii = {PONE-D-14-10302},
pmid = {24841635},
timestamp = {2015-06-29T14:34:20.000+0200},
title = {Initiation of an inflammatory response in resident intestinal lamina propria cells -use of a human organ culture model.},
url = {http://dx.doi.org/10.1371/journal.pone.0097780},
volume = 9,
year = 2014
}