ArticleAutophagy2015
Phenylbutyrate induces LL-37-dependent autophagy and intracellular killing of Mycobacterium tuberculosis in human macrophages.
Article in Autophagy, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 118 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
118 citing papers in PubMed, 1 synthesis or guideline pooled it, 168 citations in OpenAlex.
- Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)Autophagy · 2021Guideline
- Placental gene expression and antibody levels of mother-neonate pairs reveal an enhanced risk for inflammation in a helminth endemic country.Scientific reports · 2019Trial
- Trial
- Daily adjunctive therapy with vitamin DJournal of internal medicine · 2018Trial
- Significant Effects of Oral Phenylbutyrate and Vitamin D3 Adjunctive Therapy in Pulmonary Tuberculosis: A Randomized Controlled Trial.PloS one · 2015Trial
- mRNA mediated expression of novel fusion phage tail protein with antimicrobial peptides inside macrophages for targeted clearance of intracellularEmerging microbes & infections · 2026Article
- Pathogenesis of Tuberculosis: Interplay Between Host Antituberculosis Immunity and Immune Evasion Strategies ofMedComm · 2026Review
- Exploiting autophagy-targeting natural compounds for potential antimicrobial actions.Autophagy · 2026Review
- Targeting serine metabolism boosts antimycobacterial immunity during Mycobacterium tuberculosis H37Rv infection.Molecules and cells · 2026Article
- Review
- LL-37: Biological Mechanisms and Emerging Therapeutic Applications in Intestinal Disease.Immunity, inflammation and disease · 2026Review
- The dysregulation of innate immunity by Porphyromonas gingivalis in the etiology of Alzheimer's disease.Journal of internal medicine · 2026Review
- Host Defense Antimicrobial Peptides (HDPs) as Regulators of Hemostasis and Vascular Biology.Biomolecules · 2026Review
- Advancing Tuberculosis Treatment with Next-Generation Drugs and Smart Delivery Systems.Pharmaceutics · 2026Review
- Beyond VDR: Vitamin D Metabolism Genes in Tuberculosis Susceptibility, Immune Response and Implications for Diabetes Mellitus.Infection and drug resistance · 2026Review
- Serum vitamin D and calcium levels among tuberculosis patients in Southern Ethiopia: a comparative cross-sectional study.BMJ open · 2025Article
- Article
- Host-directed therapeutic targets in macrophages and their ligands against mycobacteria tuberculosis.Infection and immunity · 2025Review
- Antimicrobial Peptides of the Cathelicidin Family: Focus on LL-37 and Its Modifications.International journal of molecular sciences · 2025Review
- Unveiling the potential of antimicrobial peptides to combat Mycobacterium tuberculosis.Archives of microbiology · 2025Review
58 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 5 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
LL-37 is a human antimicrobial peptide (AMP) of the cathelicidin family with multiple activities including a mediator of vitamin D-induced autophagy in human macrophages, resulting in intracellular killing of Mycobacterium tuberculosis (Mtb). In a previous trial in healthy volunteers, we have shown that LL-37 expression and subsequent Mtb-killing can be further enhanced by 4-phenylbutyrate (PBA), also an inducer of LL-37 expression. Here, we explore a potential mechanism(s) behind PBA and LL-37-induced autophagy and intracellular killing of Mtb. Mtb infection of macrophages downregulated the expression of both the CAMP transcript and LL-37 peptide as well as certain autophagy-related genes (BECN1 and ATG5) at both the mRNA and protein levels. In addition, activation of LC3-II in primary macrophages and THP-1 cells was not detected. PBA and the active form of vitamin D3 (1,25[OH]2D3), separately or particularly in combination, were able to overcome Mtb-induced suppression of LL-37 expression. Notably, reactivation of autophagy occurred by stimulation of macrophages with PBA and promoted colocalization of LL-37 and LC3-II in autophagosomes. Importantly, PBA treatment failed to induce autophagy in Mtb-infected THP-1 cells, when the expression of LL-37 was silenced. However, PBA-induced autophagy was restored when the LL-37 knockdown cells were supplemented with synthetic LL-37. Interestingly, we have found that LL-37-induced autophagy was mediated via P2RX7 receptor followed by enhanced cytosolic free Ca(2+), and activation of AMPK and PtdIns3K pathways. Altogether, these results suggest a novel activity for PBA as an inducer of autophagy, which is LL-37-dependent and promotes intracellular killing of Mtb in human macrophages.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.