ArticlePloS one2011
Phenylbutyrate counteracts Shigella mediated downregulation of cathelicidin in rabbit lung and intestinal epithelia: a potential therapeutic strategy.
Article in PloS one, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed, 99 citations in OpenAlex.
- Functional Antibodies and Innate Immune Responses to WRSS1, a Live Oral Shigella sonnei Vaccine Candidate, in Bangladeshi Adults and Children.The Journal of infectious diseases · 2021Trial
- Significant Effects of Oral Phenylbutyrate and Vitamin D3 Adjunctive Therapy in Pulmonary Tuberculosis: A Randomized Controlled Trial.PloS one · 2015Trial
- Oral intake of phenylbutyrate with or without vitamin D3 upregulates the cathelicidin LL-37 in human macrophages: a dose finding study for treatment of tuberculosis.BMC pulmonary medicine · 2013Trial
- Efficacy of sodium butyrate adjunct therapy in shigellosis: a randomized, double-blind, placebo-controlled clinical trial.BMC infectious diseases · 2012Trial
- Antimicrobial, anti-adhesive, and anti-invasive effects of condition media derived from adipose mesenchymal stem cells against Shigella flexneri.Archives of microbiology · 2024Article
- Serotype-Dependent Inhibition ofJournal of microbiology and biotechnology · 2024Article
- 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
- Modulation of innate immunity in airway epithelium for host-directed therapy.Frontiers in immunology · 2023Review
- Large-Scale Identification of Multiple Classes of Host Defense Peptide-Inducing Compounds for Antimicrobial Therapy.International journal of molecular sciences · 2022Article
- The effect of gum Arabic supplementation on cathelicidin expression in monocyte derived macrophages in mice.BMC complementary medicine and therapies · 2022Article
- The Combined Beneficial Effects of Postbiotic Butyrate on Active Vitamin D3-Orchestrated Innate Immunity toBiomedicines · 2021Article
- Influenza Virus Infection Impairs the Gut's Barrier Properties and Favors Secondary Enteric Bacterial Infection through Reduced Production of Short-Chain Fatty Acids.Infection and immunity · 2021Article
- Eradication ofJournal of fungi (Basel, Switzerland) · 2021Article
- The Role of Butyrate in Attenuating Pathobiont-Induced Hyperinflammation.Immune network · 2020Review
- Host Directed Therapy Against Infection by Boosting Innate Immunity.Frontiers in immunology · 2020Review
- Antimicrobial and Immune-Modulatory Effects of Vitamin D Provide Promising Antibiotics-Independent Approaches to Tackle Bacterial Infections - Lessons Learnt from a Literature Survey.European journal of microbiology & immunology · 2019Review
- Novel aroylated phenylenediamine compounds enhance antimicrobial defense and maintain airway epithelial barrier integrity.Scientific reports · 2019Article
- The potential for immunoglobulins and host defense peptides (HDPs) to reduce the use of antibiotics in animal production.Veterinary research · 2018Review
- Dietary modulation of endogenous host defense peptide synthesis as an alternative approach to in-feed antibiotics.Animal nutrition (Zhongguo xu mu shou yi xue hui) · 2018Review
- High Throughput Screening for Natural Host Defense Peptide-Inducing Compounds as Novel Alternatives to Antibiotics.Frontiers in cellular and infection microbiology · 2018Article
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundCathelicidins and defensins are endogenous antimicrobial peptides (AMPs) that are downregulated in the mucosal epithelia of the large intestine in shigellosis. Oral treatment of Shigella infected rabbits with sodium butyrate (NaB) reduces clinical severity and counteracts the downregulation of cathelicidin (CAP-18) in the large intestinal epithelia.
aimsTo develop novel regimen for treating infectious diseases by inducing innate immunity, we selected sodium 4-phenylbutyrate (PB), a registered drug for a metabolic disorder as a potential therapeutic candidate in a rabbit model of shigellosis. Since acute respiratory infections often cause secondary complications during shigellosis, the systemic effect of PB and NaB on CAP-18 expression in respiratory epithelia was also evaluated.
methodsThe readouts were clinical outcomes, CAP-18 expression in mucosa of colon, rectum, lung and trachea (immunohistochemistry and real-time PCR) and release of the CAP-18 peptide/protein in stool (Western blot). PRINCIPAL
findingsSignificant downregulation of CAP-18 expression in the epithelia of rectum and colon, the site of Shigella infection was confirmed. Interestingly, reduced expression of CAP-18 was also noticed in the epithelia of lung and trachea, indicating a systemic effect of the infection. This suggests a causative link to acute respiratory infections during shigellosis. Oral treatment with PB resulted in reduced clinical illness and upregulation of CAP-18 in the epithelium of rectum. Both PB and NaB counteracted the downregulation of CAP-18 in lung epithelium. The drug effect is suggested to be systemic as intravenous administration of NaB could also upregulate CAP-18 in the epithelia of lung, rectum and colon.
conclusionOur results suggest that PB has treatment potential in human shigellosis. Enhancement of CAP-18 in the mucosal epithelia of the respiratory tract by PB or NaB is a novel discovery. This could mediate protection from secondary respiratory infections that frequently are the lethal causes in dysentery.
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