Abstract |
A promising strategy in the fight against multidrug-resistant pathogens is the induction of endogenous AMPs, with compounds such as VitD₃ and PBA. These compounds display an array of immunomodulatory effects that remain to be investigated in further detail to establish their role in the clearance of infection and possible modulation of AMP expression. Here, we have investigated the effects of VitD₃ and PBA on human monocyte-DC differentiation and found that VitD₃ and PBA promote the development of a stretched CD14⁺/CD1a⁻ DC subset. This subset produced enhanced levels of ROS and human cathelicidin; furthermore, it displayed enhanced killing capacity of Staphylococcus aureus compared with control DCs. When experiments were performed in WT and cathelicidin-deficient mice, we established that a ROS-producing, stretched DC subset was also induced in mouse-derived cells, independent of cathelicidin expression. However, in contrast to the human DCs, enhanced cathelicidin expression and enhanced antimicrobial activities were not found in the murine VitD₃/PBA DC subset. In conclusion, the results of this study show that VitD₃ and PBA induce a human DC subset that is effective against infection. These results promote further research into the use of these compounds as an antimicrobial treatment strategy.
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Authors | Anne M van der Does, Ellinor Kenne, Ella Koppelaar, Birgitta Agerberth, Lennart Lindbom |
Journal | Journal of leukocyte biology
(J Leukoc Biol)
Vol. 95
Issue 6
Pg. 883-91
(Jun 2014)
ISSN: 1938-3673 [Electronic] United States |
PMID | 24550524
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | © 2014 Society for Leukocyte Biology. |
Chemical References |
- Antimicrobial Cationic Peptides
- Cytokines
- Phenylbutyrates
- Reactive Oxygen Species
- Cholecalciferol
- 4-phenylbutyric acid
- Cathelicidins
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Topics |
- Animals
- Antimicrobial Cationic Peptides
(physiology)
- Cell Differentiation
(drug effects)
- Cells, Cultured
- Cholecalciferol
(pharmacology)
- Cytokines
(biosynthesis)
- Dendritic Cells
(cytology, drug effects, immunology)
- Humans
- Mice
- Mice, Inbred C57BL
- Monocytes
(cytology)
- Phenylbutyrates
(pharmacology)
- Reactive Oxygen Species
(metabolism)
- Cathelicidins
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