VDR and MEK-ERK dependent induction of the antimicrobial peptide cathelicidin in keratinocytes by lithocholic acid

Mark Peric, Sarah Koglin, Yvonne Dombrowski, Kathrin Gross, Eva Bradac, Thomas Ruzicka, Jürgen Schauber

Research output: Contribution to journalArticlepeer-review

25 Citations (Scopus)

Abstract

Cathelicidin is an antimicrobial peptide (AMP) and signaling molecule in innate immunity and a direct target of 1,25-dihydroxyvitamin D3 (1,25D3) in primary human keratinocytes (NHEK). The expression of cathelicidin is dysregulated in various skin diseases and its regulation differs depending on the epithelial cell type. The secondary bile acid lithocholic acid (LCA) is a ligand of the vitamin D receptor (VDR) and can carry out in vivo functions of vitamin D3. Therefore we analyzed cathelicidin mRNA- and peptide expression levels in NHEK and colonic epithelial cells (Caco-2) after stimulation with LCA. We found increased expression of cathelicidin mRNA and peptide in NHEK, in Caco-2 colon cells no effect was observed after LCA stimulation. The VDR as well as MEK-ERK signaled the upregulation of cathelicidin in NHEK induced by LCA. Collectively, our data indicate that cathelicidin induction upon LCA treatment differs in keratinocytes and colonic epithelial cells. Based on these observations LCA-like molecules targeting cathelicidin could be designed for the treatment of cutaneous diseases that are characterized by disturbed cathelicidin expression.
Original languageEnglish
Pages (from-to)3183-3187
Number of pages5
JournalMolecular Immunology
Volume46
Issue number16
Early online date05 Sep 2009
DOIs
Publication statusPublished - Oct 2009

Keywords

  • Antimicrobial Cationic Peptides
  • Caco-2 Cells
  • Calcitriol
  • Detergents
  • Enzyme Activation
  • Gene Expression Regulation
  • Humans
  • Keratinocytes
  • Lithocholic Acid
  • MAP Kinase Kinase Kinases
  • MAP Kinase Signaling System
  • RNA, Messenger
  • Skin Diseases
  • Vitamins

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