ArticleProceedings of the National Academy of Sciences of the United States of America2016
Histone deacetylase inhibition enhances antimicrobial peptide but not inflammatory cytokine expression upon bacterial challenge.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 81 citations in OpenAlex.
- Sirtuin 7 ameliorates hypertensive intestinal injury by restoring epithelial barrier integrity and gut microbiota homeostasis.Cellular and molecular life sciences : CMLS · 2026Article
- Drug resistance mechanisms inFrontiers in pharmacology · 2026Review
- Microbial short chain fatty acids: Effective histone deacetylase inhibitors in immune regulation (Review).International journal of molecular medicine · 2026Review
- Article
- The pathway of autophagy in the epigenetic landscape ofAutophagy · 2025Review
- Histone Deacetylases (HDACs) Roles in Inflammation-mediated Diseases; Current Knowledge.Cell biochemistry and biophysics · 2025Review
- Differential perception of virulence factors of uropathogenicFrontiers in immunology · 2025Article
- Identification of human host factors required for beta-defensin-2 expression in intestinal epithelial cells upon a bacterial challenge.Scientific reports · 2024Article
- Composition of Whole Grain Dietary Fiber and Phenolics and Their Impact on Markers of Inflammation.Nutrients · 2024Review
- Histone acylations as a mechanism for regulation of intestinal epithelial cells.Digestive medicine research · 2024Article
- Effects of histone acetyltransferase (HAT) and histone deacetylase (HDAC) inhibitors on proliferative, differentiative, and regenerative functions of Toll-like receptor 2 (TLR-2)-stimulated human dental pulp cells (hDPCs).Clinical oral investigations · 2023Article
- Mechanisms and regulation of defensins in host defense.Signal transduction and targeted therapy · 2023Review
- Shared genetic architecture between irritable bowel syndrome and psychiatric disorders reveals molecular pathways of the gut-brain axis.Genome medicine · 2023Article
- Repurposing HDAC inhibitors to enhance ribonuclease 4 and 7 expression and reduce urinary tract infection.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Histone deacetylase (HDAC) inhibitors- based drugs are effective to control Mycobacterium tuberculosis infection and promote the sensibility for rifampicin in MDR strain.Memorias do Instituto Oswaldo Cruz · 2023Article
- Epigenetic-Mediated Antimicrobial Resistance: Host versus Pathogen Epigenetic Alterations.Antibiotics (Basel, Switzerland) · 2022Review
- Chasing a Breath of Fresh Air in Cystic Fibrosis (CF): Therapeutic Potential of Selective HDAC6 Inhibitors to Tackle Multiple Pathways in CF Pathophysiology.Journal of medicinal chemistry · 2022Review
- Effects of Niacin on Resistance to EnterotoxigenicFrontiers in nutrition · 2022Article
- Predicting candidate therapeutic drugs for sepsis-induced acute respiratory distress syndrome based on transcriptome profiling.Bioengineered · 2021Article
- Acetyl-CoA Metabolism and Histone Acetylation in the Regulation of Aging and Lifespan.Antioxidants (Basel, Switzerland) · 2021Review
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Antimicrobial peptides (AMP) are defense effectors of the innate immunity playing a crucial role in the intestinal homeostasis with commensals and protection against pathogens. Herein we aimed to investigate AMP gene regulation by deciphering specific characteristics allowing their enhanced expression among innate immune genes, particularly those encoding proinflammatory mediators. Our emphasis was on epigenetic regulation of the gene encoding the AMP β-defensin 2 (HBD2), taken as a model of possibly specific induction, upon challenge with a commensal bacterium, compared with the proinflammatory cytokine IL-8. Using an in vitro model of colonic epithelial cells challenged with Escherichia coli K12, we showed that inhibition of histone deacetylases (HDAC) by trichostatin A dramatically enhanced induction of HBD2 expression, without affecting expression of IL-8. This mechanism was supported by an increased phosphorylation of histone H3 on serine S10, preferentially at the HBD2 promoter. This process occurred through activation of the IκB kinase complex, which also led to activation of NF-κB. Moreover, we demonstrated that NF-κB was modified by acetylation upon HDAC inhibition, partly by the histone acetyltransferase p300, and that both NF-κB and p300 supported enhanced induction of HBD2 expression. Furthermore, we identified additional genes belonging to antimicrobial defense and epithelial restitution pathways that showed a similar pattern of epigenetic control. Finally, we confirmed our finding in human colonic primary cells using an ex vivo organoid model. This work opens the way to use epigenetic pharmacology to achieve induction of epithelial antimicrobial defenses, while limiting the deleterious risk of an inflammatory response.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.