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.

Absence of neurotensin attenuates intestinal dysbiosis and inflammation by maintaining Mmp7/α‐defensin axis in diet‐induced obese mice

“…In addition, T cell receptor‐induced NF‐κB activation is negatively regulated by PKCθ in primary T cells 98 . More importantly, NT was also reported in the downregulation of NF‐κB signaling and the proinflammatory status noted in fetal‐skin dendritic cells and human skin fibroblasts 45,99 . Taken together, whether NT plays a positive or negative role in the regulation of NF‐κB activity appears to be dependent on the cell type and cellular context.…”

Neurotensin-loaded PLGA/CNC composite nanofiber membranes accelerate diabetic wound healing

“…The histological epidermal and dermal regeneration scores (Figure 3(A,B)) and ratio of the fibrotic area to the entire area ( Figure 4(A,B)) were higher in the PLGA/CNC group than in the control group, which indicated that PLGA/CNC nanofiber membranes improved diabetic wound healing by enhancing re-epithelialization and collagen deposition. After its release by nerve fibers or skin cells [14], NT may decrease the proinflammatory status in wound healing. The PLGA/CNC/NT group showed reduced expression of the inflammatory cytokines IL-1b and IL-6 ( Figures 6-8), which is consistent with previous reports.…”

“…The PLGA/CNC/NT group showed reduced expression of the inflammatory cytokines IL-1b and IL-6 ( Figures 6-8), which is consistent with previous reports. Silva et al reported that NT downregulated the activation of the cytokine IL-6 in skin dendritic cells and human skin fibroblasts [14,15]. Moura et al found that NT reduced IL-1b expression and enhanced the healing process in diabetic mice [19].…”

“…Recently, NT was found to improve wound healing. NT downregulates the proinflammatory status of human skin fibroblasts [14] and dendritic cells [15] and increases epidermal growth factor expression. Under hyperglycemic conditions, NT also modulates a chronic proinflammatory status [16].…”

The Progress of BMP4 on the Role of Ocular Development and Eye Diseases

“…BMP4 is expressed in adult corneal epithelium, corneal cells and corneal endothelial cells. Also participated in the layered corneal epithelium cells, corneal epithelial cell chemotaxis and proliferation (Zhang et al, 2015;Sandri et al, 2016;Pereira da Silva et al, 2014). This article summarized the research progress of BMP4 in different tissues of the eye and briefly reviewed the role of BMP4 in different developmental stages.…”