Anti-inflammatory cytokine TSG-6 inhibits hypertrophic scar formation in a rabbit ear model

Abstract

Hypertrophic scars are characterized by excessive fibrosis and extracellular matrix (ECM) deposition and can be functionally and cosmetically problematic; however, there are few satisfactory treatments for controlling hypertrophic scars. The inflammatory cells and cytokines involved in excessive inflammation during wound healing facilitate fibroblast proliferation and collagen deposition, leading to pathologic scar formation. TSG-6 exhibits anti-inflammatory activity. This study examined the effect of recombinant TSG-6 on inflammation in hypertrophic scars using a rabbit ear model. Six 7-mm, full-thickness, circular wounds were made on the ears of 12 rabbits. TSG-6 and PBS were intradermally injected into the right and left ear wounds, respectively. The methods of TEM and TUNEL were used to detect fibroblast apoptosis. The expressions of inflammatory factors: IL-1β, IL-6 and TNF-α, were detected by immunohistochemistry and real time polymerase chain reaction. Collagen I and III expression detected by immunohistochemistry and Masson׳s trichrome staining and SEI (scar elevation index) was used to evaluate the extent of scarring. TSG-6 injection mitigated the formation of a hypertrophic scar in the rabbit ear. TSG-6-treated wounds exhibited decreased inflammation compared with the control group, as evidenced by the lower levels of IL-1β, IL-6, TNF-α and MPO. The SEI and the synthesis of collagens I and III were significantly decreased in the TSG-6-treated scars compared with control scars. The apoptosis rate was higher in the TSG-6-treated scars. TSG-6 exhibited anti-inflammatory effects during the wound healing process and cicatrization and significantly diminished hypertrophic scar formation in a rabbit ear model.

Keywords: Animal model; Apoptosis; Chloroform (PubChem CID: 6212); Eosin (PubChem CID: 29090); Ethanol (PubChem CID: 702); Formalin (PubChem CID: 712); Glutaraldehyde (PubChem CID: 3485); Hematoxylin (PubChem CID: 10603); Hypertrophic scar; Inflammation; Isopropanol (PubChem CID: 3776); Pentobarbital (PubChem CID: 4737); Sodium citrate (PubChem CID: 6224); TSG-6; Xylene (PubChem CID: 6850715).