title: Effect of interleukin-17 on gene expression profile of fibroblasts from Crohn's disease patients.
abstract: OBJECTIVE
  The expression of interleukin (IL)-17 is upregulated in inflammatory bowel disease (IBD). Since fibroblasts are known to be responsive to IL-17, they may play a role in the modulation of inflammatory responses in IBD. Here, the effects of IL-17 on ileum and colon fibroblasts from Crohn's disease (CD) and ulcerative colitis (UC) patients are investigated, as compared to controls.
  
  
  METHODS
  Fibroblasts were isolated from surgical specimens taken from the tissue of 21 CD patients, 5 UC patients, and 14 patients undergoing surgery for colorectal carcinoma (control). The fibroblasts were cultured with and without IL-17. We performed mRNA microarray analysis on cultured fibroblasts, isolated from three CD samples and three control samples. Based on these results, the expression of IL-17 induced genes was validated in a larger selection of samples using qRT-PCR and ELISA.
  
  
  RESULTS
  The mRNA microarray showed that IL-17 induced the expression levels of various genes in fibroblasts of CD patients and controls, among which NFKBIZ, CXCL1, and CXCL6 demonstrated the most prominent response. qRT-PCR validated that IL-17 induced the expression of NFKBIZ significantly (p=0.028) in intestinal fibroblasts of CD patients. By performing an ELISA, we also discovered that, following IL-17 stimulation, CXCL1 levels were significantly increased in fibroblasts from CD patients (p=0.048). IL-17 also stimulated secretion of CXCL6 in fibroblasts from UC patients (p=0.053).
  
  
  CONCLUSIONS
  The enhanced expression of IL-17 that is observed in patients with Crohn's disease could act on intestinal fibroblasts to induce expression of transcription factor NFKBIZ and proinflammatory chemokine CXCL1. This can have consequences for fibroblast activity and neutrophil chemotaxis.
authors.affiliation: Tytgat Institute for Liver and Intestinal Research, Academic Medical Center, Amsterdam, The Netherlands. Electronic address: z.kerami@amc.uva.nl.
authors.forename: Zohra
authors.initials: Z
authors.lastname: Kerami
authors.affiliation: Tytgat Institute for Liver and Intestinal Research, Academic Medical Center, Amsterdam, The Netherlands. Electronic address: n.w.duijvis@amc.uva.nl.
authors.forename: Nicolette W
authors.initials: NW
authors.lastname: Duijvis
authors.affiliation: Tytgat Institute for Liver and Intestinal Research, Academic Medical Center, Amsterdam, The Netherlands. Electronic address: e.w.vogels@amc.uva.nl.
authors.forename: Esther W
authors.initials: EW
authors.lastname: Vogels
authors.affiliation: Tytgat Institute for Liver and Intestinal Research, Academic Medical Center, Amsterdam, The Netherlands. Electronic address: f.h.vandooren@amc.uva.nl.
authors.forename: Faas H
authors.initials: FH
authors.lastname: van Dooren
authors.affiliation: Bioinformatics Laboratory, Department of Clinical Epidemiology, Biostatistics and Bioinformatics, Academic Medical Center, Amsterdam, The Netherlands. Electronic address: p.d.moerland@amc.uva.nl.
authors.forename: Perry D
authors.initials: PD
authors.lastname: Moerland
authors.affiliation: Tytgat Institute for Liver and Intestinal Research, Academic Medical Center, Amsterdam, The Netherlands. Electronic address: a.a.tevelde@amc.uva.nl.
authors.forename: Anje A
authors.initials: AA
authors.lastname: Te Velde
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D002277:Carcinoma / Q000235:genetics / Q000378:metabolism; D002478:Cells, Cultured; D054360:Chemokine CXCL1 / Q000235:genetics / Q000378:metabolism; D054427:Chemokine CXCL6 / Q000235:genetics / Q000378:metabolism; D003093:Colitis, Ulcerative / Q000235:genetics / Q000378:metabolism; D003106:Colon; D015179:Colorectal Neoplasms / Q000235:genetics / Q000378:metabolism; D003424:Crohn Disease / Q000235:genetics* / Q000378:metabolism; D005347:Fibroblasts / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D020672:I-kappa B Proteins / Q000235:genetics; D007082:Ileum; D020381:Interleukin-17 / Q000494:pharmacology*; D009687:Nuclear Proteins / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000032:analysis*; D059467:Transcriptome / Q000187:drug effects*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C475829:CXCL1 protein, human; C515503:CXCL6 protein, human; D054360:Chemokine CXCL1; D054427:Chemokine CXCL6; D020672:I-kappa B Proteins; D020381:Interleukin-17; C417234:NFKBIZ protein, human; D009687:Nuclear Proteins; D012333:RNA, Messenger
keywords: Chemokines; Cytokines; Fibroblasts; Inflammation; Inflammatory bowel disease; Interleukin 17