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Role of Toll Like Receptors in Irritable Bowel Syndrome: Differential Mucosal Immune Activation According to the Disease Subtype
Open accessAbstract
BACKGROUND: The irritable bowel syndrome (IBS) is a functional gastrointestinal disorder whose pathogenesis is not completely understood. Its high prevalence and the considerable effects on quality of life make IBS a disease with high social cost. Recent studies suggest that low grade mucosal immune activation, increased intestinal permeability and the altered host-microbiota interactions that modulate innate immune response, contribute to the pathophysiology of IBS. However, the understanding of the precise molecular pathophysiology remains largely unknown. METHODOLOGY AND FINDINGS: In this study our objective was to evaluate the TLR expression as a key player in the innate immune response, in the colonic mucosa of IBS patients classified into the three main subtypes (with constipation, with diarrhea or mixed). TLR2 and TLR4 mRNA expression was assessed by real time RT-PCR while TLRs protein expression in intestinal epithelial cells was specifically assessed by flow cytometry and immunofluorescence. Mucosal inflammatory cytokine production was investigated by the multiplex technology. Here we report that the IBS-Mixed subgroup displayed a significant up-regulation of TLR2 and TLR4 in the colonic mucosa. Furthermore, these expressions were localized in the epithelial cells, opening new perspectives for a potential role of epithelial cells in host-immune interactions in IBS. In addition, the increased TLR expression in IBS-M patients elicited intracellular signaling pathways resulting in increased expression of the mucosal proinflammatory cytokines IL-8 and IL1β. CONCLUSIONS: Our results provide the first evidence of differential expression of TLR in IBS patients according to the disease subtype. These results offer further support that microflora plays a central role in the complex pathophysiology of IBS providing novel pharmacological targets for this chronic gastrointestinal disorder according to bowel habits.
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“Increased expression of proinflammatory cytokines may be elicited through interactions between bacterial components and pattern recognition receptors including TLRs such as TLR2 and TLR4 that have been associated with IBS90.”
From The gut Microbiome in adult and pediatric functional gastrointestinal disorders (2019) · cites this paper as [90]
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Metadata
- Authors
- Belmonte, L., Beutheu Youmba, S., Bertiaux-Vandaële, N., Antonietti, M., Lecleire, S., Zalar, A., Gourcerol, G., Leroi, A.-M., Déchelotte, P., Coëffier, M., & Ducrotté, P.
- Affiliations
- Academia Nacional de Medicina (AR)
- Centre Hospitalier Universitaire de Rouen (FR)
- Inserm (FR)
- Corresponding author
- Belmonte, Liliana
- Venue
- PLoS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2012-08-17
- Volume
- 7
- Issue
- 8
- Pages
- e42777
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC3461726
- OpenAlex
- W2080290298
- Cited by
- 126
- References
- 38
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 9 · 2023: 3 · 2022: 15 · 2021: 10 · 2020: 11 · 2019: 6 · 2018: 10 · 2017: 7 · 2016: 11 · 2015: 14 · 2014: 18 · 2013: 10
- FWCI
- 13.04
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- PLoS ONE (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Topics
- Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Keywords
- irritable bowel syndrome, Toll-like receptors, TLR2, TLR4, colonic mucosa, IBS subtypes, intestinal epithelial cells, mucosal inflammation, inflammatory cytokines, interleukin-8, IL-1β, host-microbiota interactions, innate immune response, intestinal permeability
- MeSH terms
- Adult, Aged, Colon, Female, Humans, Intestinal Mucosa, Male, Middle Aged, RNA, Messenger, Up-Regulation, Gene Expression, Case-Control Studies, Cytokines, Inflammation Mediators, Lipopolysaccharide Receptors, Irritable Bowel Syndrome, PPAR gamma, Toll-Like Receptor 2, Toll-Like Receptor 4
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