IL-10 alleviates lipopolysaccharide-induced skin scarring via
IL-10R/STAT3 axis regulating TLR4/NF-κB pathway in dermal fibroblasts
Abstract
Background and Purpose: Hypertrophic scar (HS) is a serious fibrotic
skin disease. The roles of bacterial contamination and prolonged
inflammation in wound were considered to be significant. IL-10 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, explore the possible mechanism in scar
formation. Experimental Approach: RT-qPCR, Western blotting,
histochemistry, immunostaining, ELISA array, electron microscope,
fibroblast-populated collagen lattice (FPCL) and a rabbit ear scar model
were used to investigate and validate the effect of IL-10 on
LPS-stimulated scar formation. Key Results: 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 upregulate the expression of TLR4, pp65,
Col I, Col III and α-SMA in NSFs, but IL-10 could downregulate their
expression in both HSFs and LPS-induced NSFs. Blocking IL-10 receptor
(IL-10R) or the phosphorylation of STAT3, their expression was
upregulated. 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. Conclutions and
Implications: Our study suggests that IL-10 may improve LPS-induced
harmful to wound healing, reduce scar contracture and scar formation via
IL-10R/STAT3 axis regulating TLR4/NF-κB pathway in dermal fibroblasts by
reducing ECM proteins deposition and the conversion of HSFs to NSFs.
Therefore, the downregulation of inflammation may be a better option for
improving scar quality, and become potential therapeutic targets for
scarring.