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

doi:10.4155/fmc-2016-0085

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

Houston Methodist

Research output: Contribution to journal › Article › peer-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 language	English (US)
Pages (from-to)	2033-2046
Number of pages	14
Journal	Future Medicinal Chemistry
Volume	8
Issue number	17
DOIs	https://doi.org/10.4155/fmc-2016-0085
State	Published - Nov 2016

Keywords

caffeic acid phenethyl ester
Candida
innate immune response
p21 kinase
propolis

ASJC Scopus subject areas

Molecular Medicine
Pharmacology
Drug Discovery

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

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.",

keywords = "caffeic acid phenethyl ester, Candida, innate immune response, p21 kinase, propolis",

author = "Coleman, {Jeffrey J.} and Tomomi Komura and Julia Munro and Wu, {Michael P.} and Busanelli, {Rakhee R.} and Koehler, {Angela N.} and M{\'e}ryl Thomas and Wagner, {Florence F.} and Holson, {Edward B.} and Eleftherios Mylonakis",

note = "Funding Information: This research was made possible by NIH funding from the National Institute of Allergy and Infectious Diseases P01 AI083214 to E Mylonakis and National Cancer Institute RC2 CA148399 to AN Koehler, and a grant from the Rhode Island Medical Foundation to JJ Coleman. Publisher Copyright: {\textcopyright} 2016 Future Science Ltd.",

year = "2016",

month = nov,

doi = "10.4155/fmc-2016-0085",

language = "English (US)",

volume = "8",

pages = "2033--2046",

journal = "Future Medicinal Chemistry",

issn = "1756-8919",

publisher = "Future Science",

number = "17",

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T1 - The immunomodulatory activity of caffeic acid phenethyl ester in Caenorhabditis elegans is mediated by the CED-10 (Rac-1)/PAK1 pathway

AU - Coleman, Jeffrey J.

AU - Komura, Tomomi

AU - Munro, Julia

AU - Wu, Michael P.

AU - Busanelli, Rakhee R.

AU - Koehler, Angela N.

AU - Thomas, Méryl

AU - Wagner, Florence F.

AU - Holson, Edward B.

AU - Mylonakis, Eleftherios

N1 - Funding Information: This research was made possible by NIH funding from the National Institute of Allergy and Infectious Diseases P01 AI083214 to E Mylonakis and National Cancer Institute RC2 CA148399 to AN Koehler, and a grant from the Rhode Island Medical Foundation to JJ Coleman. Publisher Copyright: © 2016 Future Science Ltd.

PY - 2016/11

Y1 - 2016/11

N2 - 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.

AB - 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.

KW - caffeic acid phenethyl ester

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KW - innate immune response

KW - p21 kinase

KW - propolis

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

Abstract

Keywords

ASJC Scopus subject areas

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