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Mucosal cytokine imbalance in irritable bowel syndrome
Abstract
OBJECTIVE: To systematically examine mucosal biopsies for differences in cytokine gene expression and protein secretion. MATERIAL AND METHODS: The study included 59 females with irritable bowel syndrome (IBS) and 39, otherwise healthy, female volunteers presenting for colonoscopy. Colonic biopsies from subsets were studied by microarray analysis (IBS, n=9; controls, n=8), quantitative reverse transcription-polymerase chain reaction (qRT-PCR) (IBS, n=22; controls, n=21), and ex vivo biopsy culture (IBS, n=28, controls, n=10). Biopsies from patients with active colitis were used as inflammatory disease controls. RESULTS: While gene array analysis revealed extensive overlapping between controls and IBS patients, reduced expression of genes linked to chemokine function was evident among the IBS patients alone. Differential expression was confirmed by qRT-PCR or ex vivo biopsy culture for 5 out of 6 selected genes. Reduced secretion of chemokines (IL-8, CXCL-9 and MCP-1) but not pro-inflammatory cytokines (TNF-alpha, IL-6 and IL-1beta) was established on the basis of the ex vivo biopsy cultures. These findings were in marked contrast to the IBD patients who demonstrated increased production of both chemokines and pro-inflammatory cytokines. CONCLUSIONS: Despite the expected heterogeneity of the disorder, differences in mucosal chemokine signalling were evident in this cross-sectional study of IBS patients at the level of both gene expression and protein secretion, with IBS patients demonstrating a consistent deficit in the expression and secretion of chemokines known to play a critical role in mucosal defence.
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“Ex vivo examination of cytokine secretion by the colon failed to show elevation of proinflammatory cytokines or chemokines in patients with IBS compared with controls (102).”
From Intestinal microbiota and immune function in the pathogenesis of irritable bowel syndrome (2013) · cites this paper as [102]
In the citing paper
“However, in this study a decreased level of mRNA encoding the anti-inflammatory IL-10 gene was observed, as well as an altered IL-10:IL-12 ratio in colonic biopsies from patients with IBS compared with controls, supporting the hypothesis that patients with IBS have a dysfunctional immunological response in the mucosa.”
From Intestinal microbiota and immune function in the pathogenesis of irritable bowel syndrome (2013) · cites this paper as [102]
In the citing paper
“In contrast, a study by Macsharry and colleagues (102) found reduced levels of IL-1β mRNA in colonic biopsies from patients with IBS.”
From Intestinal microbiota and immune function in the pathogenesis of irritable bowel syndrome (2013) · cites this paper as [102]
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Metadata
- Authors
- Macsharry, J., O'Mahony, L., Fanning, A., Bairead, E., Sherlock, G., Tiesman, J., Fulmer, A., Kiely, B., Dinan, T. G., Shanahan, F., & Quigley, E. M. M.
- Affiliations
- Alimentary Health (Ireland) (IE)
- University College Cork (IE)
- Procter & Gamble (United States) (US)
- Corresponding author
- Quigley, Eamonn M. M.
- Venue
- Scandinavian Journal of Gastroenterology
- Publisher
- Informa UK Limited
- Published
- 2008-01
- Volume
- 43
- Issue
- 12
- Pages
- 1467-1476
- ISSN
- 0036-5521 (ISSN-L)
- 1502-7708
- OpenAlex
- W2116909437
- Cited by
- 174
- References
- 40
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 8 · 2023: 6 · 2022: 2 · 2021: 9 · 2020: 10 · 2019: 5 · 2018: 6 · 2017: 13 · 2016: 11 · 2015: 10 · 2014: 15 · 2013: 13 · 2012: 20
- FWCI
- 13.81
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Scandinavian Journal of Gastroenterology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
- Health Sciences › Medicine › Gastroenterology › Inflammatory Bowel Disease
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Keywords
- irritable bowel syndrome, colonic mucosa, cytokine gene expression, chemokines, interleukin-8, CXCL9, MCP-1, inflammatory cytokines, mucosal protection, inflammatory bowel disease, colonoscopic biopsy
- MeSH terms
- Adolescent, Adult, Aged, Colonoscopy, Female, Humans, Intestinal Mucosa, Middle Aged, Tumor Necrosis Factor-alpha, Interleukin-6, Gene Expression, Cytokines, Interleukin-8, Chemokine CCL2, Reverse Transcriptase Polymerase Chain Reaction, Irritable Bowel Syndrome, Interleukin-1beta, Chemokine CXCL9
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