title: Neurotensin modulates the migratory and inflammatory response of macrophages under hyperglycemic conditions.
abstract: Diabetic foot ulcers (DFUs) are characterized by an unsatisfactory inflammatory and migratory response. Skin inflammation involves the participation of many cells and particularly macrophages. Macrophage function can be modulated by neuropeptides; however, little is known regarding the role of neurotensin (NT) as a modulator of macrophages under inflammatory and hyperglycemic conditions. RAW 264.7 cells were maintained at 10/30 mM glucose, stimulated with/without LPS (1 μg/mL), and treated with/without NT(10 nM). The results show that NT did not affect macrophage viability. However, NT reverted the hyperglycemia-induced impair in the migration of macrophages. The expression of IL-6 and IL-1β was significantly increased under 10 mM glucose in the presence of NT, while IL-1β and IL-12 expression significantly decreased under inflammatory and hyperglycemic conditions. More importantly, high glucose modulates NT and NT receptor expression under normal and inflammatory conditions. These results highlight the effect of NT on cell migration, which is strongly impaired under hyperglycemic conditions, as well as its effect in decreasing the proinflammatory status of macrophages under hyperglycemic and inflammatory conditions. These findings provide new insights into the potential therapeutic role of NT in chronic wounds, such as in DFU, characterized by a deficit in the migratory properties of cells and a chronic proinflammatory status.
authors.affiliation: Center for Neuroscience and Cell Biology, University of Coimbra, 3004-517 Coimbra, Portugal.
authors.forename: Liane I F
authors.initials: LI
authors.lastname: Moura
authors.forename: Lucília
authors.initials: L
authors.lastname: Silva
authors.forename: Ermelindo C
authors.initials: EC
authors.lastname: Leal
authors.forename: Ana
authors.initials: A
authors.lastname: Tellechea
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: Cruz
authors.forename: Eugénia
authors.initials: E
authors.lastname: Carvalho
mesh_terms: D000818:Animals; D002460:Cell Line; D002465:Cell Movement; D016207:Cytokines / Q000276:immunology*; D006943:Hyperglycemia / Q000188:drug therapy / Q000276:immunology*; D007249:Inflammation / Q000188:drug therapy / Q000276:immunology*; D008262:Macrophage Activation / Q000187:drug effects / Q000276:immunology*; D008264:Macrophages / Q000187:drug effects / Q000276:immunology*; D051379:Mice; D009496:Neurotensin / Q000008:administration & dosage*
chemical_list: D016207:Cytokines; D009496:Neurotensin