Format

Send to

Choose Destination
See comment in PubMed Commons below
Nat Commun. 2015 Oct 13;6:8369. doi: 10.1038/ncomms9369.

Tamoxifen augments the innate immune function of neutrophils through modulation of intracellular ceramide.

Author information

  • 1Department of Pediatrics, University of California, San Diego, La Jolla, California 92093, USA.
  • 2Department of Pharmacology, University of California, San Diego, La Jolla, California 92093, USA.
  • 3Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla, California 92093, USA.
  • 4Department of Medicine, University of California, San Diego, La Jolla, California 92093, USA.
  • 5Rady Children's Hospital, San Diego, California 92123, USA.

Abstract

Tamoxifen is a selective oestrogen receptor modulator widely used for the treatment of breast cancer. In addition to its activity as an oestrogen receptor agonist/antagonist, tamoxifen also modulates sphingolipid biosynthesis, which has been shown to play an important role in the regulation of neutrophil activity. Here, we find that tamoxifen stimulation enhances several pro-inflammatory pathways in human neutrophils, including chemotaxis, phagocytosis and neutrophil extracellular trap (NET) formation. The enhancement of NET production occurs via a ceramide/PKCζ-mediated pathway, and treatment with synthetic ceramide is sufficient to promote NET formation. Pretreatment of human neutrophils with tamoxifen boosts neutrophil bactericidal capacity against a variety of pathogens in vitro and enhances clearance of the leading human pathogen methicillin-resistant Staphylococcus aureus in vivo. Our results suggest that tamoxifen, and the lipid signalling pathways it modulates, merit further exploration as targets for boosting host innate immune function.

PMID:
26458291
PMCID:
PMC4610010
DOI:
10.1038/ncomms9369
[PubMed - indexed for MEDLINE]
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Nature Publishing Group Icon for PubMed Central
    Loading ...
    Support Center