Table of Contents Author Guidelines Submit a Manuscript
Oxidative Medicine and Cellular Longevity
Volume 2017 (2017), Article ID 4157213, 12 pages
Research Article

Role of Protein Kinase C and Nox2-Derived Reactive Oxygen Species Formation in the Activation and Maturation of Dendritic Cells by Phorbol Ester and Lipopolysaccharide

1Department of Dermatology, Medical Center of the Johannes Gutenberg University, Mainz, Germany
2Center for Cardiology/Cardiology 1, Laboratory of Molecular Cardiology, Medical Center of the Johannes Gutenberg University, Mainz, Germany
3Center for Thrombosis and Hemostasis (CTH), Medical Center of the Johannes Gutenberg University, Mainz, Germany

Correspondence should be addressed to Angelika Reske-Kunz and Andreas Daiber

Received 18 November 2016; Revised 7 February 2017; Accepted 8 February 2017; Published 28 March 2017

Academic Editor: Leopoldo Aguilera-Aguirre

Copyright © 2017 Judith Stein et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Aims. Activation/maturation of dendritic cells (DCs) plays a central role in adaptive immune responses by antigen processing and (cross-) activation of T cells. There is ongoing discussion on the role of reactive oxygen species (ROS) in these processes and with the present study we investigated this enigmatic pathway. Methods and Results. DCs were cultured from precursors in the bone marrow of mice (BM-DCs) and analyzed for ROS formation, maturation, and T cell stimulatory capacity upon stimulation with phorbol ester (PDBu) and lipopolysaccharide (LPS). LPS stimulation of BM-DCs caused maturation with moderate intracellular ROS formation, whereas PDBu treatment resulted in maturation with significant ROS formation. The NADPH oxidase inhibitors apocynin/VAS2870 and genetic gp91phox deletion both decreased the ROS signal in PDBu-stimulated BM-DCs without affecting maturation and T cell stimulatory capacity of BM-DCs. In contrast, the protein kinase C inhibitors chelerythrine/Gö6983 decreased PDBu-stimulated ROS formation in BM-DCs as well as maturation. Conclusion. Obviously Nox2-dependent ROS formation in BM-DCs is not always required for their maturation or T cell stimulatory potential. PDBu/LPS-triggered BM-DC maturation rather relies on phosphorylation cascades. Our results question the role of oxidative stress as an essential “danger signal” for BM-DC activation, although we cannot exclude contribution by other ROS sources.