Histone-deacetylase inhibitors induce the cathelicidin LL-37 in gastrointestinal cells
Abstract
Unlabelled Histone-deacetylase (HDAC) -inhibitors enhance acetylation of core proteins and this is linked to formation of transcriptionally active chromatin in various cells. In this study, the effect of HDAC inhibitors (butyrate, trichostatin A (TSA)) on the expression of the cathelicidin LL-37 in colon, gastric and hepatocellular cells was investigated.Methods LL-37 expression was assessed in colon, gastric and hepatocellular cancer cells after treatment with HDAC-inhibitors. In parallel, histone H4 and HMGN2, a non-histone protein, acetylation was evaluated. In addition, the intracellular signalling pathway MEK-ERK was explored.Results In contrast to normal colon epithelial cells, gastrointestinal cancer cells lacked LL-37 expression. LL-37 was induced following treatment with HDAC-inhibitors in all investigated cell lines. This induction was time-dependent in butyrate-treated cells while TSA exerted a transient effect. Induction of LL-37 by butyrate was paralleled by acetylation of the histone H4 and the non-histone HMGN2. Again, TSA resulted in transient acetylation. Furthermore, inhibition of MEK-ERK blocked HDAC inhibitor-induced LL-37 expression in colonic and gastric cells.Conclusions We have previously shown that butyrate induces LL-37 in colon epithelial cells. In the present study, we demonstrate that cathelicidin expression is modulated by HDAC-inhibitors in various gastrointestinal cells including gastric and hepatocellular cells. This is paralleled by changes in the acetylation of distinct core proteins suggesting a common regulatory mechanism of cathelicidin LL-37 regulation in these cells.
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Microbial metabolites are integral for promoting immune responses in the gut against pathogens, including inducing secretion of IL-18 and defensins.
“microbial metabolites are integral for promoting immune responses in the gut against pathogens, including inducing secretion of IL-18 (36) and defensins (37, 38)”
From Respiratory viral infection-induced microbiome alterations and secondary bacterial pneumonia. (2018) · cites this paper as [38]
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- Authors
- Schauber, J., Iffland, K., Frisch, S., Kudlich, T., Schmausser, B., Eck, M., Menzel, T., Gostner, A., Lührs, H., & Scheppach, W.
- Affiliations
- University of Würzburg (DE)
- Corresponding author
- Schauber, Jürgen
- ORCID
- Kudlich, Theodor
- Venue
- Molecular Immunology
- Publisher
- Elsevier BV
- Published
- 2004-07
- Volume
- 41
- Issue
- 9
- Pages
- 847-854
- ISSN
- 0161-5890 (ISSN-L)
- OpenAlex
- W1987590582
- Cited by
- 109
- References
- 39
- Citations by year
- 2026: 2 · 2024: 1 · 2023: 2 · 2022: 6 · 2021: 3 · 2020: 3 · 2019: 4 · 2018: 7 · 2017: 3 · 2016: 4 · 2015: 6 · 2014: 6 · 2013: 10 · 2012: 12
- FWCI
- 1.31
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Molecular Immunology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Bundesministerium für Bildung und Forschung
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Histone Deacetylase Inhibitors Research
- Life Sciences › Immunology and Microbiology › Microbiology › Antimicrobial Peptides and Activities
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Keywords
- histone deacetylase inhibitors, cathelicidin LL-37, butyrate, trichostatin A, histone H4 acetylation, MEK/ERK signaling, colonic epithelial cells, gastric cancer cells
- MeSH terms
- Animals, Butyrates, Gastrointestinal Neoplasms, Humans, Hydroxamic Acids, Phylogeny, Signal Transduction, Mitogen-Activated Protein Kinases, MAP Kinase Kinase Kinases, Antimicrobial Cationic Peptides, Gastrointestinal Tract, Cathelicidins, Histone Deacetylase Inhibitors
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