Limits...
5-hydroxytryptamine modulates migration, cytokine and chemokine release and T-cell priming capacity of dendritic cells in vitro and in vivo.

Müller T, Dürk T, Blumenthal B, Grimm M, Cicko S, Panther E, Sorichter S, Herouy Y, Di Virgilio F, Ferrari D, Norgauer J, Idzko M - PLoS ONE (2009)

Bottom Line: Additionally, 5-HT influenced chemokine release by human monocyte-derived DCs: production of the potent Th1 chemoattractant IP-10/CXCL10 was inhibited in mature DCs, whereas CCL22/MDC secretion was up-regulated in both immature and mature DCs.Furthermore, DCs matured in the presence of 5-HT switched to a high IL-10 and low IL-12p70 secreting phenotype.Consistently, 5-HT favoured the outcome of a Th2 immune response both in vitro and in vivo.

View Article: PubMed Central - PubMed

Affiliation: Department of Pneumology, University Hospital Freiburg, Freiburg, Germany.

ABSTRACT
Beside its well described role in the central and peripheral nervous system 5-hydroxytryptamine (5-HT), commonly known as serotonin, is also a potent immuno-modulator. Serotoninergic receptors (5-HTR) are expressed by a broad range of inflammatory cell types, including dendritic cells (DCs). In this study, we aimed to further characterize the immuno-biological properties of serotoninergic receptors on human monocyte-derived DCs. 5-HT was able to induce oriented migration in immature but not in LPS-matured DCs via activation of 5-HTR(1) and 5-HTR(2) receptor subtypes. Accordingly, 5-HT also increased migration of pulmonary DCs to draining lymph nodes in vivo. By binding to 5-HTR(3), 5-HTR(4) and 5-HTR(7) receptors, 5-HT up-regulated production of the pro-inflammatory cytokine IL-6. Additionally, 5-HT influenced chemokine release by human monocyte-derived DCs: production of the potent Th1 chemoattractant IP-10/CXCL10 was inhibited in mature DCs, whereas CCL22/MDC secretion was up-regulated in both immature and mature DCs. Furthermore, DCs matured in the presence of 5-HT switched to a high IL-10 and low IL-12p70 secreting phenotype. Consistently, 5-HT favoured the outcome of a Th2 immune response both in vitro and in vivo. In summary, our study shows that 5-HT is a potent regulator of human dendritic cell function, and that targeting serotoninergic receptors might be a promising approach for the treatment of inflammatory disorders.

Show MeSH

Related in: MedlinePlus

5-HT inhibits the release of IP 10/CXCL10 and stimulates MDC/CCL22 secretion in DCs.Immature and mature DCs were left untreated or were stimulated with the indicated concentration of 5-HT for 24 h (A–B). CXCL10 and CCL22 release was measured by ELISA. The results are expressed as mean pg/ml±SEM (n = 4).
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC2714071&req=5

pone-0006453-g002: 5-HT inhibits the release of IP 10/CXCL10 and stimulates MDC/CCL22 secretion in DCs.Immature and mature DCs were left untreated or were stimulated with the indicated concentration of 5-HT for 24 h (A–B). CXCL10 and CCL22 release was measured by ELISA. The results are expressed as mean pg/ml±SEM (n = 4).

Mentions: Immature DCs produce high levels of CCL22/MDC and very low levels of IP-10/CXCL10, whereas in LPS-matured DCs the secretion of both CCL22 and CXCL10 is up-regulated (Fig. 2). When DCs were treated with LPS in the presence of 5-HT, a dose dependent inhibition of CXCL10 production was observed (Fig. 2A), while the production of CCL22 was increased. In addition 5-HT also enhanced the secretion of CCL22 in immature DCs (Fig. 2B).


5-hydroxytryptamine modulates migration, cytokine and chemokine release and T-cell priming capacity of dendritic cells in vitro and in vivo.

Müller T, Dürk T, Blumenthal B, Grimm M, Cicko S, Panther E, Sorichter S, Herouy Y, Di Virgilio F, Ferrari D, Norgauer J, Idzko M - PLoS ONE (2009)

5-HT inhibits the release of IP 10/CXCL10 and stimulates MDC/CCL22 secretion in DCs.Immature and mature DCs were left untreated or were stimulated with the indicated concentration of 5-HT for 24 h (A–B). CXCL10 and CCL22 release was measured by ELISA. The results are expressed as mean pg/ml±SEM (n = 4).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2714071&req=5

pone-0006453-g002: 5-HT inhibits the release of IP 10/CXCL10 and stimulates MDC/CCL22 secretion in DCs.Immature and mature DCs were left untreated or were stimulated with the indicated concentration of 5-HT for 24 h (A–B). CXCL10 and CCL22 release was measured by ELISA. The results are expressed as mean pg/ml±SEM (n = 4).
Mentions: Immature DCs produce high levels of CCL22/MDC and very low levels of IP-10/CXCL10, whereas in LPS-matured DCs the secretion of both CCL22 and CXCL10 is up-regulated (Fig. 2). When DCs were treated with LPS in the presence of 5-HT, a dose dependent inhibition of CXCL10 production was observed (Fig. 2A), while the production of CCL22 was increased. In addition 5-HT also enhanced the secretion of CCL22 in immature DCs (Fig. 2B).

Bottom Line: Additionally, 5-HT influenced chemokine release by human monocyte-derived DCs: production of the potent Th1 chemoattractant IP-10/CXCL10 was inhibited in mature DCs, whereas CCL22/MDC secretion was up-regulated in both immature and mature DCs.Furthermore, DCs matured in the presence of 5-HT switched to a high IL-10 and low IL-12p70 secreting phenotype.Consistently, 5-HT favoured the outcome of a Th2 immune response both in vitro and in vivo.

View Article: PubMed Central - PubMed

Affiliation: Department of Pneumology, University Hospital Freiburg, Freiburg, Germany.

ABSTRACT
Beside its well described role in the central and peripheral nervous system 5-hydroxytryptamine (5-HT), commonly known as serotonin, is also a potent immuno-modulator. Serotoninergic receptors (5-HTR) are expressed by a broad range of inflammatory cell types, including dendritic cells (DCs). In this study, we aimed to further characterize the immuno-biological properties of serotoninergic receptors on human monocyte-derived DCs. 5-HT was able to induce oriented migration in immature but not in LPS-matured DCs via activation of 5-HTR(1) and 5-HTR(2) receptor subtypes. Accordingly, 5-HT also increased migration of pulmonary DCs to draining lymph nodes in vivo. By binding to 5-HTR(3), 5-HTR(4) and 5-HTR(7) receptors, 5-HT up-regulated production of the pro-inflammatory cytokine IL-6. Additionally, 5-HT influenced chemokine release by human monocyte-derived DCs: production of the potent Th1 chemoattractant IP-10/CXCL10 was inhibited in mature DCs, whereas CCL22/MDC secretion was up-regulated in both immature and mature DCs. Furthermore, DCs matured in the presence of 5-HT switched to a high IL-10 and low IL-12p70 secreting phenotype. Consistently, 5-HT favoured the outcome of a Th2 immune response both in vitro and in vivo. In summary, our study shows that 5-HT is a potent regulator of human dendritic cell function, and that targeting serotoninergic receptors might be a promising approach for the treatment of inflammatory disorders.

Show MeSH
Related in: MedlinePlus