The immunomodulatory activity of caffeic acid phenethyl ester in Caenorhabditis elegans is mediated by the CED-10 (Rac-1)/PAK1 pathway

Jeffrey J. Coleman, Tomomi Komura, Julia Munro, Michael P. Wu, Rakhee R. Busanelli, Angela N. Koehler, Méryl Thomas, Florence F. Wagner, Edward B. Holson, Eleftherios Mylonakis

Research output: Contribution to journalArticlepeer-review

15 Scopus citations

Abstract

Aim: Caffeic acid (3,4-dihydroxycinnamic acid) phenethyl ester (CAPE), the major constituent of propolis, is able to increase the survival of the nematode Caenorhabditis elegans after infection with the fungal pathogen Candida albicans. Results: CAPE increases the expression of several antimicrobial proteins involved in the immune response to C. albicans. Structural derivatives of CAPE were synthesized to identify structure-activity relationships and decrease metabolic liability, ultimately leading to a compound that has similar efficacy, but increased in vivo stability. The CED-10(Rac-1)/PAK1 pathway was essential for immunomodulation by CAPE and was a critical component involved in the immune response to fungal pathogens. Conclusion: Caenorhabditis elegans is an efficient heterologous host to evaluate immunomodulatory compounds and identify components of the pathway(s) involved in the mode of action of compounds.

Original languageEnglish (US)
Pages (from-to)2033-2046
Number of pages14
JournalFuture Medicinal Chemistry
Volume8
Issue number17
DOIs
StatePublished - Nov 2016

Keywords

  • Candida
  • caffeic acid phenethyl ester
  • innate immune response
  • p21 kinase
  • propolis

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology
  • Drug Discovery

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