Cited by 242Immune Response and InflammationInflammatory Bowel DiseaseGastrointestinal motility and disorders

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Intestinal myofibroblasts in innate immune responses of the intestine

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Otte, Jan-Michel, Rosenberg, Ian M, Podolsky, Daniel K·2003·Gastroenterology

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Abstract

Background & aims Intestinal myofibroblasts are known to respond to inflammatory signals and may play a role in Crohn's disease-associated fibrosis. However, putative involvement by myofibroblasts in innate immune responses as part of intestinal host defense has not been characterized. We therefore analyzed expression and regulation of toll-like receptors (TLRs) in colonic human myofibroblasts (CCD-18) and primary human colonic myofibroblasts in comparison with human lung myofibroblasts (CCD-37).Methods Expression of TLRs (1-10) and NOD 1 and 2 was assessed before and after stimulation with either lipopolysaccharide (LPS) or lipoteichoic acid (LTA) by using a custom microarray, reverse-transcription polymerase chain reaction, Northern blot and Western blot analysis, and immunohistochemistry. Activation of signaling pathways, translocation of p65, and secretion of interleukin (IL)-8 were determined.Results Messenger RNAs encoding for TLR1-9, as well as NOD1 and NOD2, were amplified from cultured and primary human intestinal myofibroblasts. After stimulation with LPS or LTA, a 1.5-4.2-fold up-regulation of TLRs (2, 3, 4, 6, 7) and elements of the signaling cascade (MyD88, TIR domain-containing adapter protein [TIRAP]) was observed. CCD-18 and CCD-37 cells expressed TLR 2 and 4 protein, which were located primarily on the cell membrane. Stimulation with LTA or LPS resulted in activation of the mitogen-activated protein kinases pathway, nuclear translocation of p65, and significantly increased IL-8 secretion.Conclusions Bacterial components directly activate intestinal myofibroblasts expressing TLRs. These cells may therefore participate in innate immune responses by sensing and responding to bacterial products that have penetrated into the subepithelial compartment.

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Authors: Otte, J.-M., Rosenberg, I. M., & Podolsky, D. K.
Affiliations: Harvard University (US)
Corresponding author: Podolsky, Daniel K
ORCID: Podolsky, Daniel K
Venue: Gastroenterology
Publisher: Elsevier BV
Published: 2003-06
Volume: 124
Issue: 7
Pages: 1866-1878
ISSN: 0016-5085 (ISSN-L)
DOI: 10.1016/s0016-5085(03)00403-7
OpenAlex: W1984107869
Cited by: 242
References: 63
Citations by year: 2026: 3 · 2025: 6 · 2024: 7 · 2023: 5 · 2022: 6 · 2021: 9 · 2020: 11 · 2019: 10 · 2018: 15 · 2017: 7 · 2016: 6 · 2015: 17 · 2014: 12 · 2013: 11 · 2012: 16
FWCI: 4.00
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Gastroenterology (publishedVersion)
PubMed (publishedVersion)
Funders: National Institute of Diabetes and Digestive and Kidney Diseases (P30DK 433-51, R01 DK 60049, R01DK060049, P30DK043351)
Topics: Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
Health Sciences › Medicine › Gastroenterology › Inflammatory Bowel Disease
Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
Keywords: intestinal myofibroblasts, innate immunity, Toll-like receptors, NOD1, NOD2, lipopolysaccharide, lipoteichoic acid, MyD88, TIRAP, MAPK signaling, p65 nuclear translocation, interleukin-8, colonic myofibroblasts, lung myofibroblasts, bacterial sensing
MeSH terms: Cells, Cultured, Colon, Fibroblasts, Humans, Immunity, Innate, Intestinal Mucosa, Lipopolysaccharides, Membrane Glycoproteins, Receptors, Cell Surface, RNA, Messenger, Teichoic Acids, Inflammatory Bowel Diseases, Interleukin-8, Reverse Transcriptase Polymerase Chain Reaction, Oligonucleotide Array Sequence Analysis, Mitogen-Activated Protein Kinases, Toll-Like Receptors, Toll-Like Receptor 1, Toll-Like Receptor 2

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Intestinal myofibroblasts in innate immune responses of the intestine

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