Synergistic Stimulation with Different TLR7 Ligands Modulates Gene Expression Patterns in the Human Plasmacytoid Dendritic Cell Line CAL-1
Joint Authors
Hilbert, Tobias
Steinhagen, Folkert
Weisheit, Christina
Klaschik, Sven
Hoeft, Andreas
Baumgarten, Georg
Source
Issue
Vol. 2015, Issue 2015 (31 Dec. 2015), pp.1-13, 13 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2015-12-06
Country of Publication
Egypt
No. of Pages
13
Main Subjects
Abstract EN
Objective.
TLR7 ligation in plasmacytoid dendritic cells is promising for the treatment of cancer, allergy, and infectious diseases; however, high doses of ligands are required.
We hypothesized that the combination of structurally different TLR7 ligands exponentiates the resulting immune response.
Methods.
CAL-1 (human pDC line) cells were incubated with the TLR7-specific adenine analog CL264 and single-stranded 9.2s RNA.
Protein secretion was measured by ELISA.
Microarray technique was used to detect modified gene expression patterns upon synergistic stimulation, revealing underlying functional groups and networks.
Cell surface binding properties were studied using FACS analysis.
Results.
CL264 in combination with 9.2s RNA significantly enhanced cytokine and interferon secretion to supra-additive levels.
This effect was due to a stronger stimulation of already regulated genes (by monostimulation) as well as to recruitment of thus far unregulated genes.
Top scoring canonical pathways referred to immune-related processes.
Network analysis revealed IL-1β, IL-6, TNF, and IFN-β as major regulatory nodes, while several minor regulatory nodes were also identified.
Binding of CL264 to the cell surface was enhanced by 9.2s RNA.
Conclusion.
Structurally different TLR7 ligands act synergistically on gene expression patterns and on the resulting inflammatory response.
These data could impact future strategies optimizing TLR7-targeted drug design.
American Psychological Association (APA)
Hilbert, Tobias& Steinhagen, Folkert& Weisheit, Christina& Baumgarten, Georg& Hoeft, Andreas& Klaschik, Sven. 2015. Synergistic Stimulation with Different TLR7 Ligands Modulates Gene Expression Patterns in the Human Plasmacytoid Dendritic Cell Line CAL-1. Mediators of Inflammation،Vol. 2015, no. 2015, pp.1-13.
https://search.emarefa.net/detail/BIM-1072658
Modern Language Association (MLA)
Hilbert, Tobias…[et al.]. Synergistic Stimulation with Different TLR7 Ligands Modulates Gene Expression Patterns in the Human Plasmacytoid Dendritic Cell Line CAL-1. Mediators of Inflammation No. 2015 (2015), pp.1-13.
https://search.emarefa.net/detail/BIM-1072658
American Medical Association (AMA)
Hilbert, Tobias& Steinhagen, Folkert& Weisheit, Christina& Baumgarten, Georg& Hoeft, Andreas& Klaschik, Sven. Synergistic Stimulation with Different TLR7 Ligands Modulates Gene Expression Patterns in the Human Plasmacytoid Dendritic Cell Line CAL-1. Mediators of Inflammation. 2015. Vol. 2015, no. 2015, pp.1-13.
https://search.emarefa.net/detail/BIM-1072658
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1072658