The Role of IL-6 in Skin Fibrosis and Cutaneous Wound Healing

Johnson, Blair Z.; Stevenson, Andrew; Prêle, Cecilia M.; Fear, Mark W.; Wood, Fiona

doi:10.3390/biomedicines8050101

Cited by 289 publications

(229 citation statements)

References 147 publications

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“…Assessing the absolute expression output, the UC-MSCs seem to be the more potent cells based on the classic example of the growth factor FGF-2 production as previously described [ 15 ]. As other researchers described previously, we observed a similar cytokine expression pattern, such as IP-10 [ 61 , 62 ] and increased IL-6, IL-17, and TNF-alpha for reparative cells [ 63 ], in secretory cytokine profiling from both MSCs. MSC-secreted cytokines are involved in proinflammatory reactions, cell differentiation, activation, and proliferation of leukocytes (i.e., macrophages), endothelial cells, keratinocytes, and fibroblasts.…”

Section: Discussionsupporting

confidence: 85%

Biological characteristics of stem cells derived from burned skin—a comparative study with umbilical cord stem cells

et al. 2021

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Introduction Burned human skin, which is routinely excised and discarded, contains viable mesenchymal stromal/stem cells (burn-derived mesenchymal stromal/stem cells; BD-MSCs). These cells show promising potential to enable and aid wound regeneration. However, little is known about their cell characteristics and biological function. Objectives This study had two aims: first, to assess critical and cellular characteristics of BD-MSCs and, second, to compare those results with multipotent well-characterized MSCs from Wharton’s jelly of human umbilical cords (umbilical cord mesenchymal stromal/stem cells, UC-MSCs). Methods BD- and UC-MSCs were compared using immunophenotyping, multi-lineage differentiation, seahorse analysis for glycolytic and mitochondrial function, immune surface markers, and cell secretion profile assays. Results When compared to UC-MSCs, BD-MSCs demonstrated a lower mesenchymal differentiation capacity and altered inflammatory cytokine secretomes at baseline and after stimulation with lipopolysaccharides. No significant differences were found in population doubling time, colony formation, cell proliferation cell cycle, production of reactive oxygen species, glycolytic and mitochondrial function, and in the expression of major histocompatibility complex I and II and toll-like receptor (TLR). Importance, translation This study reveals valuable insights about MSCs obtained from burned skin and show comparable cellular characteristics with UC-MSCs, highlighting their potentials in cell therapy and skin regeneration.

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Section: Discussionsupporting

confidence: 85%

Biological characteristics of stem cells derived from burned skin—a comparative study with umbilical cord stem cells

et al. 2021

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“…Summarizing, the exposure to H 2 O 2 disturbed keratinocyte proliferation and IL-6 gene expression and production. The administration of Futura 75 extract proved to be able to restore, albeit partially, the levels of this key cytokine in skin physiology [ 42 ].…”

Section: Resultsmentioning

confidence: 99%

Metabolomic Profile and Antioxidant/Anti-Inflammatory Effects of Industrial Hemp Water Extract in Fibroblasts, Keratinocytes and Isolated Mouse Skin Specimens

et al. 2021

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Industrial hemp is a multiuse crop whose phytocomplex includes terpenophenolics and flavonoids. In the present study, the phenolic and terpenophenolic compounds were assayed in the water extract of the hemp variety Futura 75. Protective effects were also investigated in human fibroblast and keratinocytes and isolate mouse skin specimens, which were exposed to hydrogen peroxide and/or to the extract (1–500 µg/mL). The results of phytochemical analysis suggested the cannabidiol, cannabidiolic acid and rutin as the prominent phytocompounds. In the in vitro system represented by human keratinocytes and fibroblasts, the hemp extract was found to be able to protect cells from cytotoxicity and apoptosis induced by oxidative stress. Moreover, modulatory effects on IL-6, a key mediator in skin proliferation, were found. In isolated rat skin, the extract reduced hydrogen peroxide-induced l-dopa turnover, prostaglandin-E2 production and the ratio kynurenine/tryptpophan, thus corroborating anti-inflammatory/antioxidant effects. The in silico docking studies also highlighted the putative interactions between cannabidiol, cannabidiolic acid and rutin with tyrosinase and indoleamine-2,3-dioxygenase, involved in l-dopa turnover and tryptophan conversion in kynurenine, respectively. In conclusion, the present findings showed the efficacy of hemp water extract as a skin protective agent. This could be partly related to the extract content in cannabidiol, cannabidiolic acid and rutin.

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“…In addition to IL-8 (Fig. S4 ) 17 , IL-6 is another pro-inflammatory cytokine known to play a key role in acute inflammation and is pivotal for the timely resolution of cutaneous wound healing 37 . Dysregulation of IL-6 signaling can lead to either fibrosis or a failure to heal.…”

Section: Resultsmentioning

confidence: 99%

Octenidine-based hydrogel shows anti-inflammatory and protease-inhibitory capacities in wounded human skin

Seiser

Janker

Zila

et al. 2021

Sci Rep

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Octenidine dihydrochloride (OCT) is a widely used antiseptic molecule, promoting skin wound healing accompanied with improved scar quality after surgical procedures. However, the mechanisms by which OCT is contributing to tissue regeneration are not yet completely clear. In this study, we have used a superficial wound model by tape stripping of ex vivo human skin. Protein profiles of wounded skin biopsies treated with OCT-containing hydrogel and the released secretome were analyzed using liquid chromatography-mass spectrometry (LC–MS) and enzyme-linked immunosorbent assay (ELISA), respectively. Proteomics analysis of OCT-treated skin wounds revealed significant lower levels of key players in tissue remodeling as well as reepithelization after wounding such as pro-inflammatory cytokines (IL-8, IL-6) and matrix-metalloproteinases (MMP1, MMP2, MMP3, MMP9) when compared to controls. In addition, enzymatic activity of several released MMPs into culture supernatants was significantly lower in OCT-treated samples. Our data give insights on the mode of action based on which OCT positively influences wound healing and identified anti-inflammatory and protease-inhibitory activities of OCT.

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The Role of IL-6 in Skin Fibrosis and Cutaneous Wound Healing

Cited by 289 publications

References 147 publications

Biological characteristics of stem cells derived from burned skin—a comparative study with umbilical cord stem cells

Biological characteristics of stem cells derived from burned skin—a comparative study with umbilical cord stem cells

Metabolomic Profile and Antioxidant/Anti-Inflammatory Effects of Industrial Hemp Water Extract in Fibroblasts, Keratinocytes and Isolated Mouse Skin Specimens

Octenidine-based hydrogel shows anti-inflammatory and protease-inhibitory capacities in wounded human skin

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