The neuropeptide Substance P facilitates the transition from an inflammatory to proliferation phase‐associated responses in dermal fibroblasts

Abstract

The wound healing process is a product of three successive and overlapping phases of inflammation, proliferation and remodelling. Considerable efforts have been invested in deconstructing the intercellular crosstalk that orchestrates tissue repair, and we investigated the role of neuropeptides released from peripheral neurons upon injury in mediating these interactions. Amongst the most abundant of these neuropeptides secreted by nerves in the skin, is Substance P (SP). Given the role of dermal fibroblasts in coordinating multiple processes in the wound healing program, the effect of SP on human dermal fibroblasts of different ages was evaluated. The use of a substrate that recapitulates the mechanical properties of the in vivo tissue revealed novel effects of SP on dermal fibroblasts, including a block in inflammatory cytokine expression. Moreover, SP can promote expression of some extracellular matrix components and generates signals that regulate angiogenesis. Interestingly, the response of fibroblasts to SP was reduced concomitant with donor age. Altogether, SP acts to inhibit the inflammatory responses and promote proliferation‐associated responses in an age‐dependent manner in dermal fibroblasts, suggesting a role as a molecular switch between the inflammatory and proliferative phases of the wound healing response.

Hydrolyzed Collagen Induces an Anti-Inflammatory Response That Induces Proliferation of Skin Fibroblast and Keratinocytes

“…It was reported that cytokines play a key role in the initiation, severity, and duration of the inflammatory process of the skin [ 15 , 16 ]. In addition, the central involvement of fibroblasts [ 15 ] and keratinocytes [ 16 ] in this process was demonstrated.…”

“…It was reported that cytokines play a key role in the initiation, severity, and duration of the inflammatory process of the skin [ 15 , 16 ]. In addition, the central involvement of fibroblasts [ 15 ] and keratinocytes [ 16 ] in this process was demonstrated. Therefore, the present study showed for the first time that hydrolyzed collagen inhibited the LPS-induced release of an important and classical panel of pro-inflammatory cytokines (IL-1β, IL-6, IL-8, TNF-α) from human skin fibroblasts (CCD-1072Sk) and human keratinocytes (hKT-nh-skp-KT0026).…”

“…Thus, here we discuss the role of each of these cytokines in the modulation of skin inflammation and healing. In fact, IL-1β was reported as a potent pro-inflammatory cytokine that is synthesized and released by keratinocytes upon activation of Staphylococcus aureus [ 15 ] and by fibroblast upon activation of Cutibacterium acnes [ 17 ], and its increased levels are related to cell death and damage. The present study showed for the first time that hydrolyzed collagen reduced IL-1β secretion by skin fibroblasts and keratinocytes.…”