title: Neurotensin decreases the proinflammatory status of human skin fibroblasts and increases epidermal growth factor expression.
abstract: Fibroblasts colonization into injured areas during wound healing (WH) is responsible for skin remodelling and is also involved in the modulation of inflammation, as fibroblasts are immunologically active. Herein, we aimed to determine neurotensin effect on the immunomodulatory profile of fibroblasts, both in homeostatic and inflammatory conditions. Neurotensin mediated responses occurred through NTR1 or NTR3 receptors, while under inflammatory conditions NTR1 expression increase seemed to modulate neurotensin responses. Among different immunomodulatory genes, CCL11, IL-8, and IL-6 were the most expressed genes, while CCL4 and EGF were the less expressed genes. After neurotensin exposure, IL-8 mRNA expression was increased while CCL11 was decreased, suggesting a proinflammatory upregulation and chemoattractant ability downregulation of fibroblasts. Under inflammatory conditions, gene expression was significantly increased. After neurotensin exposure, CCL4 and IL-6 mRNA expression were decreased while CCL11 was increased, suggesting again a decrease in the chemoattractant capacity of fibroblasts and in their proinflammatory status. Furthermore, the expression of EGF, a crucial growth factor for skin cells proliferation and WH, was increased in all conditions. Overall, neurotensin, released by nerve fibers or skin cells, may be involved in the decrease of the chemotaxis and the proinflammatory status in the proliferation and remodelling phases of WH.
authors.affiliation: Faculdade de Ciências e Tecnologia, Universidade de Coimbra, 3000-456 Coimbra, Portugal ; Centro de Neurociências e Biologia Celular, Universidade de Coimbra, 3004-504 Coimbra, Portugal.
authors.forename: Lucília
authors.identifier: 0000-0002-4889-7799
authors.initials: L
authors.lastname: Pereira da Silva
authors.affiliation: Centro de Neurociências e Biologia Celular, Universidade de Coimbra, 3004-504 Coimbra, Portugal ; Faculdade de Farmácia, Universidade de Coimbra, 3000-548 Coimbra, Portugal.
authors.forename: Bruno
authors.initials: B
authors.lastname: Miguel Neves
authors.affiliation: Faculdade de Ciências e Tecnologia, Universidade de Coimbra, 3000-456 Coimbra, Portugal ; Centro de Neurociências e Biologia Celular, Universidade de Coimbra, 3004-504 Coimbra, Portugal.
authors.forename: Liane
authors.identifier: 0000-0003-4264-6865
authors.initials: L
authors.lastname: Moura
authors.affiliation: Centro de Neurociências e Biologia Celular, Universidade de Coimbra, 3004-504 Coimbra, Portugal ; Faculdade de Farmácia, Universidade de Coimbra, 3000-548 Coimbra, Portugal.
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: Cruz
authors.affiliation: Centro de Neurociências e Biologia Celular, Universidade de Coimbra, 3004-504 Coimbra, Portugal ; Associação Portuguesa de Diabetes (APDP), 1250-189 Lisboa, Portugal.
authors.forename: Eugénia
authors.initials: E
authors.lastname: Carvalho