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LL-37

Cathelicidin, hCAP-18, FALL-39, CAP-18

Quick Stats
Studies 2230
Trials 95
Score 3
2008 pubmed 100 citations

PU.1 and bacterial metabolites regulate the human gene CAMP encoding antimicrobial peptide LL-37 in colon epithelial cells.

Termén. Stefan S; Tollin. Maria M; Rodriguez. Eduardo E; Sveinsdóttir. Sigrún H SH; Jóhannesson. Bjarki B; Cederlund. Andreas A; Sjövall. Jan J; Agerberth. Birgitta B; Gudmundsson. Gudmundur H GH

Key Findings

  • PU.1 transcription factor binds to the CAMP promoter and drives LL‑37 expression in colon epithelial cells
  • A conserved second intron works together with the promoter to enhance CAMP transcription
  • Lithocholic acid and butyrate each increase CAMP transcription, with additive effects when combined

Practical Outcomes

  • Increasing butyrate—via high‑fiber foods, resistant starch, or butyrate supplements—may modestly raise LL‑37 levels and support gut barrier function. Lithocholic acid also boosts LL‑37 but is a secondary bile acid that can be toxic at high levels, so it’s not a safe supplement for most people. Overall, the study provides a mechanistic reason to prioritize butyrate‑rich strategies for gut health, but direct dosing guidelines are not established.

Summary

Researchers found that a gut‑derived molecule called butyrate, and another called lithocholic acid, can turn up the production of the antimicrobial peptide LL‑37 in colon cells. This boost is controlled by a protein called PU.1. While the work was done in a lab cell line, it hints that boosting butyrate through diet or supplements might help strengthen gut defenses, though the role of lithocholic acid is less clear and may carry risks.

Abstract

Mammalian antimicrobial peptides contribute to the protective barrier against microbes at epithelial surfaces. This study focuses on the promoter of the human CAMP gene, encoding the antimicrobial peptide LL-37, and induction of the gene in the colonic epithelial cell line HT-29. CAMP promoter segments were inserted in front of a luciferase reporter in order to identify regulatory regions. A transcription promoting region was identified and the transcription factor PU.1 of the Ets family was recruited to this region as shown by ChIP analysis. This ties PU.1 to the regulation of human innate epithelial defences for the first time. In addition, the conserved second intron was found to exert a transcription enhancing effect in cooperation with the 3' end of the proximal promoter, and the importance of two upstream AUG codons was examined. Moreover, we here demonstrate that lithocholic acid enhances CAMP transcription, and does so additively with butyrate. Thus, a crosstalk between bacteria and host epithelia of the gut could be partially mediated via these two bacterial products to obtain gut homeostasis.

Study Information

Provider

pubmed

Year

2008

Date

2008-07-26T00:00:00.000Z

DOI

10.1016/j.molimm.2008.06.020

Citations

100

References

34