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Nitric oxide sustains IL-1β expression in human dendritic cells enhancing their capacity to induce IL-17-producing T-cells.

Obregon C, Graf L, Chung KF, Cesson V, Nicod LP - PLoS ONE (2015)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Pneumology Service, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Lausanne, Switzerland.

ABSTRACT
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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Related in: MedlinePlus

Cytokine release is dependent on NO. concentration.DCs were stimulated for 23 h with different concentrations of DPTA NONOate 10 minutes before maturation with LPS (100ng/ml). Cytokines were measured using Luminex system as described in Material and Methods: (A) IL-10, (B) IL-12p70 and (C) TNF-α. Data are expressed as means ±SEM of 6 independent experiments. *P < 0.05.
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pone.0120134.g001: Cytokine release is dependent on NO. concentration.DCs were stimulated for 23 h with different concentrations of DPTA NONOate 10 minutes before maturation with LPS (100ng/ml). Cytokines were measured using Luminex system as described in Material and Methods: (A) IL-10, (B) IL-12p70 and (C) TNF-α. Data are expressed as means ±SEM of 6 independent experiments. *P < 0.05.

Mentions: To determine whether NO. is able to modulate the release of cytokines from matured DCs, and therefore influence initiation and development of inflammation towards a pro-inflammatory or anti-inflammatory state, we used the NO donor, DPTA NONOate, which is able to release NO. with a half-life of 5h at neutral pH. For these experiments, DPTA NONOate was added at different concentrations to immature DC cultures 10 min before the induction of maturation with LPS. Concerning the concentration of LPS, 100 ng has shown to be sufficient to stimulate DCs, inducing low cell death (apoptosis/necrosis) (S1 Fig). As already shown, LPS-matured DCs released a mixed pattern of Th1 and Th2 cytokines with high amounts of IL-10, IL-12 and TNF-α. Under our co-stimulatory conditions of DPTA NONOate and LPS, when a high concentration of DPTA NONOate was added before DC maturation, the release of TNF-α, as well as IL-10, was non-significantly modulated (Fig. 1A and C). On the other hand, the release of IL-12 was inhibited with DPTA NONOate at 0.6mM (Fig. 1B). These results show that NO. act predominantly on IL-12 release and may modulate an inflammatory or anti-inflammatory process depending on the concentration used.


Nitric oxide sustains IL-1β expression in human dendritic cells enhancing their capacity to induce IL-17-producing T-cells.

Obregon C, Graf L, Chung KF, Cesson V, Nicod LP - PLoS ONE (2015)

Cytokine release is dependent on NO. concentration.DCs were stimulated for 23 h with different concentrations of DPTA NONOate 10 minutes before maturation with LPS (100ng/ml). Cytokines were measured using Luminex system as described in Material and Methods: (A) IL-10, (B) IL-12p70 and (C) TNF-α. Data are expressed as means ±SEM of 6 independent experiments. *P < 0.05.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4390375&req=5

pone.0120134.g001: Cytokine release is dependent on NO. concentration.DCs were stimulated for 23 h with different concentrations of DPTA NONOate 10 minutes before maturation with LPS (100ng/ml). Cytokines were measured using Luminex system as described in Material and Methods: (A) IL-10, (B) IL-12p70 and (C) TNF-α. Data are expressed as means ±SEM of 6 independent experiments. *P < 0.05.
Mentions: To determine whether NO. is able to modulate the release of cytokines from matured DCs, and therefore influence initiation and development of inflammation towards a pro-inflammatory or anti-inflammatory state, we used the NO donor, DPTA NONOate, which is able to release NO. with a half-life of 5h at neutral pH. For these experiments, DPTA NONOate was added at different concentrations to immature DC cultures 10 min before the induction of maturation with LPS. Concerning the concentration of LPS, 100 ng has shown to be sufficient to stimulate DCs, inducing low cell death (apoptosis/necrosis) (S1 Fig). As already shown, LPS-matured DCs released a mixed pattern of Th1 and Th2 cytokines with high amounts of IL-10, IL-12 and TNF-α. Under our co-stimulatory conditions of DPTA NONOate and LPS, when a high concentration of DPTA NONOate was added before DC maturation, the release of TNF-α, as well as IL-10, was non-significantly modulated (Fig. 1A and C). On the other hand, the release of IL-12 was inhibited with DPTA NONOate at 0.6mM (Fig. 1B). These results show that NO. act predominantly on IL-12 release and may modulate an inflammatory or anti-inflammatory process depending on the concentration used.

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Pneumology Service, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Lausanne, Switzerland.

ABSTRACT
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.

Show MeSH
Related in: MedlinePlus