IL‐10 alleviates lipopolysaccharide‐induced skin scarring via IL‐10R/STAT3 axis regulating TLR4/NF‐κB pathway in dermal fibroblasts

Abstract

Hypertrophic scar (HS) is a severe fibrotic skin disease. It has always been a major problem in clinical treatment, mainly because its pathogenesis has not been well understood. The roles of bacterial contamination and prolonged wound inflammation were considered significant. IL‐10 is a potent anti‐inflammatory cytokine and plays a pivotal role in wound healing and scar formation. Here, we investigate whether IL‐10 alleviates lipopolysaccharide (LPS)‐induced inflammatory response and skin scarring and explore the possible mechanism of scar formation. Our results showed that the expression of TLR4 and pp65 was higher in HS and HS‐derived fibroblasts (HSFs) than their counterpart normal skin (NS) and NS‐derived fibroblasts (NSFs). LPS could up‐regulate the expression of TLR4, pp65, Col I, Col III and α‐SMA in NSFs, but IL‐10 could down‐regulate their expression in both HSFs and LPS‐induced NSFs. Blocking IL‐10 receptor (IL‐10R) or the phosphorylation of STAT3, their expression was up‐regulated. In addition, in vitro and in vivo models results showed that IL‐10 could alleviate LPS‐induced fibroblast‐populated collagen lattice (FPCL) contraction and scar formation. Therefore, IL‐10 alleviates LPS‐induced skin scarring via IL‐10R/STAT3 axis regulating TLR4/NF‐κB pathway in dermal fibroblasts by reducing ECM proteins deposition and the conversion of fibroblasts to myofibroblasts. Our results indicate that IL‐10 can alleviate the LPS‐induced harmful effect on wound healing, reduce scar contracture, scar formation and skin fibrosis. Therefore, the down‐regulation of inflammation may lead to a suitable scar outcome and be a better option for improving scar quality.

In Vitro and Clinical Evaluation of Cannabigerol (CBG) Produced via Yeast Biosynthesis: A Cannabinoid with a Broad Range of Anti-Inflammatory and Skin Health-Boosting Properties

“…CBG significantly increased HAS2 expression 2.1-fold, while CBD did not reach significance and increased FGF2 expression ~3.5 times better than CBD (10.5-fold vs. 2.9-fold). Lastly, CBG was found to significantly upregulate interleukin-10 (IL-10), a potent anti-inflammatory cytokine [22], by 2.9-fold while CBD had no significant effect (Figure 1b).…”

Microneedle-Mediated Biomimetic Cyclodextrin Metal Organic Frameworks for Active Targeting and Treatment of Hypertrophic Scars

“…Therefore, inhibiting the intracellular signal of TGF-β1/Smad is an important means of improving the proliferation of HSFs . STAT3 is involved in the inhibition of cell apoptosis and tissue fibrosis and is overexpressed in HS tissues . Inhibition of STAT3 can reduce excessive synthesis of the extracellular matrix and reduce the symptoms of HS29.…”

Therapeutic Strategies by Regulating Interleukin Family to Suppress Inflammation in Hypertrophic Scar and Keloid

“…Lipopolysaccharide (LPS) could induce NFs into HFs and participate in the formation of HS by TLR4/NF-κB pathway (J. Shi et al, 2021), and promote the production of inflammatory molecules (J. Wang et al, 2011).…”

“…The addition of IL-10 inhibited the inflammation and fibroblast filled collagen lattice (FPCL) contracture induced by LPS, which was associated with regulating the IL-10R/STAT3 axis of TLR4/NF-κ B pathway in skin fibroblasts (J. Shi et al, 2021). In the rabbit ear hypertrophic scar model, BMSCs modified with IL-10 inhibited the expression of TNF-α, IL-6 and IL-1 β mRNA through JNK/NF-κ B pathway, which significantly reduced the wound healing time, scar area and height (Xie et al, 2020).…”