Nitric Oxide Sustains IL-1β Expression in Human Dendritic Cells Enhancing Their Capacity to Induce IL-17–Producing T-Cells

The role played by lung dendritic cells (DCs) which are influenced by external antigens and by their redox state in controlling inflammation is unclear. We studied the role played by nitric oxide (NO) in DC maturation and function. Human DCs were stimulated with a long-acting NO donor, DPTA NONOate,...

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Published in:PloS one Vol. 10; no. 4; p. e0120134
Main Authors: Obregon, Carolina, Graf, Lukas, Chung, Kian Fan, Cesson, Valerie, Nicod, Laurent P.
Format: Journal Article
Language:English
Published: United States Public Library of Science 08.04.2015
Public Library of Science (PLoS)
Subjects:
Alkenes - pharmacology
Antigens
Benzoates - pharmacology
Cell differentiation
Cytokines
Dendritic cells
Dendritic Cells - drug effects
Dendritic Cells - immunology
Dendritic Cells - metabolism
Differentiation (biology)
Dose-Response Relationship, Drug
Gene expression
Gene Expression Regulation - drug effects
Helper cells
Humans
Imidazoles - pharmacology
Inflammation
Interleukin 12
Interleukin 17
Interleukin 23
Interleukin 6
Interleukin-17 - biosynthesis
Interleukin-17 - metabolism
Interleukin-1beta - genetics
Lipopolysaccharides
Lungs
Lymphocytes T
Maturation
Nitric oxide
Nitric Oxide - pharmacology
Redox properties
T-Lymphocytes - drug effects
T-Lymphocytes - immunology
T-Lymphocytes - metabolism
Time Factors
ISSN:1932-6203, 1932-6203
Online Access:Get full text
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Summary:The role played by lung dendritic cells (DCs) which are influenced by external antigens and by their redox state in controlling inflammation is unclear. We studied the role played by nitric oxide (NO) in DC maturation and function. Human DCs were stimulated with a long-acting NO donor, DPTA NONOate, prior to exposure to lipopolysaccharide (LPS). Dose-and time-dependent experiments were performed with DCs with the aim of measuring the release and gene expression of inflammatory cytokines capable of modifying T-cell differentiation, towardsTh1, Th2 and Th17 cells. NO changed the pattern of cytokine release by LPS-matured DCs, dependent on the concentration of NO, as well as on the timing of its addition to the cells during maturation. Addition of NO before LPS-induced maturation strongly inhibited the release of IL-12, while increasing the expression and release of IL-23, IL-1β and IL-6, which are all involved in Th17 polarization. Indeed, DCs treated with NO efficiently induced the release of IL-17 by T-cells through IL-1β. Our work highlights the important role that NO may play in sustaining inflammation during an infection through the preferential differentiation of the Th17 lineage.
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Conceived and designed the experiments: CO LN. Performed the experiments: LG VC CO. Analyzed the data: LG VC CO KFC. Contributed reagents/materials/analysis tools: CO LN. Wrote the paper: KFC CO LN VC LG.
Competing Interests: The authors have declared that no competing interests exist.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0120134