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

Stefan Termén, Maria Tollin, Eduardo Rodriguez, Sigrún H. Sveinsdóttir, Bjarki Jóhannesson, Andreas Cederlund, Jan Sjövall, Birgitta Agerberth, Gudmundur H. Gudmundsson*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

67 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)3947-3955
Number of pages9
JournalMolecular Immunology
Volume45
Issue number15
DOIs
Publication statusPublished - Sep 2008

Bibliographical note

Funding Information:
The authors thank B. Olsson for cell culture support, Dr. C. Svanholm for an introduction to transfection, and Dr. L. Bandholtz and Dr. D.X. Johansson for discussion. Supported by the Swedish Research Council (K2005-16X-11217-11A), Cancerfonden the Swedish Foundation for International Cooperation in Research and Higher Education (STINT), Petrus and Augusta Hedlund's Foundation, Torsten and Ragnar Söderberg's Foundation, University of Iceland research fund and The Icelandic Centre for Research (RANNÍS).

Other keywords

  • Cathelicidin
  • Gene regulation
  • Host-microbe crosstalk
  • Mucosal immunity
  • Nuclear receptors

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