Effect of interleukin-17 on gene expression profile of fibroblasts from Crohn's disease patients

• DOI: 10.1016/j.crohns.2014.02.009
• Publication Date: 2014-03-19T18:46:21Z
• Authors: Zohra Kerami; Nicolette W. Duijvis; Esther W. Vogels; Faas H. van Dooren; Perry D. Moerland; Anje A. te Velde
• Keywords: 0303 health sciences; Chemokine CXCL6; Colon; Chemokine CXCL1; Carcinoma; Interleukin-17; Nuclear Proteins; Fibroblasts; 3. Good health; 03 medical and health sciences; Crohn Disease; Ileum; Humans; Colitis, Ulcerative; I-kappa B Proteins; RNA, Messenger; Colorectal Neoplasms; Transcriptome; Cells, Cultured; Adaptor Proteins, Signal Transducing; Oligonucleotide Array Sequence Analysis

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.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.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).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.