title: Neurotensin downregulates the pro-inflammatory properties of skin dendritic cells and increases epidermal growth factor expression.
abstract: In the last decades some reports reveal the neuropeptide neurotensin (NT) as an immune mediator in the Central Nervous System and in the gastrointestinal tract, however its effects on skin immunity were not identified. The present study investigates the effect of NT on signal transduction and on pro/anti-inflammatory function of skin dendritic cells. Furthermore, we investigated how neurotensin can modulate the inflammatory responses triggered by LPS in skin dendritic cells. We observed that fetal-skin dendritic cells (FSDCs) constitutively express NTR1 and NTR3 (neurotensin receptors) and that LPS treatment induces neurotensin expression. In addition, NT downregulated the activation of the inflammatory signaling pathways NF-κB and JNK, as well as, the expression of the cytokines IL-6, TNF-α, IL-10 and the vascular endothelial growth factor (VEGF), while the survival pathway ERK and epidermal growth factor (EGF) were upregulated. Simultaneous dendritic cells exposure to LPS and NT induced a similar cytokine profile to that one induced by NT alone. However, cells pre-treated with NT and then incubated with LPS, completely changed their cytokine profile, upregulating the cytokines tested, without changes on growth factor expression. Overall, our results could open new perspectives in the design of new therapies for skin diseases, like diabetic wound healing, where neuropeptide exposure seems to be beneficial.
authors.affiliation: Faculdade de Ciências e Tecnologia, Universidade de Coimbra, Coimbra, Portugal.
authors.forename: Lucília
authors.initials: L
authors.lastname: da Silva
authors.forename: Bruno Miguel
authors.initials: BM
authors.lastname: Neves
authors.forename: Liane
authors.initials: L
authors.lastname: Moura
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: Cruz
authors.forename: Eugénia
authors.initials: E
authors.lastname: Carvalho
mesh_terms: D000818:Animals; D048430:Cell Shape / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000187:drug effects* / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects; D004815:Epidermal Growth Factor / Q000235:genetics* / Q000378:metabolism; D005333:Fetus / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D018836:Inflammation Mediators / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D009496:Neurotensin / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology* / Q000502:physiology; D018028:Receptors, Neurotensin / Q000235:genetics / Q000378:metabolism; D012867:Skin / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D018836:Inflammation Mediators; D008070:Lipopolysaccharides; D018028:Receptors, Neurotensin; D009496:Neurotensin; D004815:Epidermal Growth Factor