Initiation of an inflammatory response in resident intestinal lamina propria cells -use of a human organ culture model.
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.
Institute of Immunology, University Hospital Heidelberg, Heidelberg, Germany.
Jutta
J
Schröder-Braunstein
Institute of Immunology, University Hospital Heidelberg, Heidelberg, Germany.
Judith
J
Gras
Division of Theoretical Bioinformatics, German Cancer Research Center (DKFZ), Heidelberg, Germany.
Benedikt
B
Brors
Institute of Immunology, University Hospital Heidelberg, Heidelberg, Germany.
Sonja
S
Schwarz
Institute of Immunology, University Hospital Heidelberg, Heidelberg, Germany; Department of Anesthesiology, University Hospital Heidelberg, Heidelberg, Germany.
Timea
T
Szikszai
Institute of Pathology, University Hospital Heidelberg, Heidelberg, Germany.
Felix
F
Lasitschka
Institute of Immunology, University Hospital Heidelberg, Heidelberg, Germany.
Guido
G
Wabnitz
Institute of Immunology, University Hospital Heidelberg, Heidelberg, Germany.
Antje
A
Heidtmann
Institute of Immunology, University Hospital Heidelberg, Heidelberg, Germany; Department of Gastroenterology, Hepatology, and Endocrinology, Hannover Medical School, Hannover, Germany.
Young-Seon
YS
Lee
Institute of Immunology, University Hospital Heidelberg, Heidelberg, Germany; Department of Surgery, University Hospital Heidelberg, Heidelberg, Germany.
Serin
S
Schiessling
Department of Surgery, University Hospital Heidelberg, Heidelberg, Germany.
Christine
C
Leowardi
Department of Surgery, University Hospital Heidelberg, Heidelberg, Germany.
Mohammed
M
Al-Saeedi
Department of Surgery, University Hospital Heidelberg, Heidelberg, Germany.
Alexis
A
Ulrich
Department of Surgery, Salem Hospital, Heidelberg, Germany.
Antonia
A
Engelke
Department of Surgery, St. Vincentius Hospital, Speyer, Germany.
Johannes
J
Winter
Institute of Immunology, University Hospital Heidelberg, Heidelberg, Germany.
Yvonne
Y
Samstag
Institute of Immunology, University Hospital Heidelberg, Heidelberg, Germany.
Thomas
T
Giese
Institute of Immunology, University Hospital Heidelberg, Heidelberg, Germany.
Stefan
S
Meuer
D003106:Colon / Q000166:cytology / Q000276:immunology*; D019295:Computational Biology; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D006801:Humans; D020287:In Situ Nick-End Labeling; D007249:Inflammation / Q000276:immunology*; D018836:Inflammation Mediators / Q000378:metabolism*; D061346:Laser Capture Microdissection; D046228:Microarray Analysis; D009092:Mucous Membrane / Q000166:cytology / Q000276:immunology*; D009924:Organ Culture Techniques / Q000379:methods*; D060888:Real-Time Polymerase Chain Reaction
D018836:Inflammation Mediators