The therapeutic effect of Interleukin-18 on hypertrophic scar via inducing fas ligand expression

Abstract Objective Among downstream interleukin-18 (IL-18) targets, Fas ligand (FasL) in particular, has been strongly implicated in many diseases. Our study aims to explore the role of IL-18 in hypertrophic scar via enhancing FasL expression. Methods IL-18 expression in hypertrophic scar tissues and normal tissues were explored by immunohistochemistry, qRT-PCR and Western blotting, and the expression of IL-18 in normal skin fibroblasts and hypertrophic scar fibroblasts by immunofluorescence. Hypertrophic scar fibroblasts treated with recombinant human IL-18 (rhIL-18) were subjected to MTT, Annexin V-FITC/PI, qRT-PCR, ELISA and western blotting. In the hypertrophic scar of rabbit ears, rhIL-18 was injected to determine the histological changes via HE and Masson stainings. Besides, the scars were rated based on contour and overall severity using a visual analog scale scores (VAS). Results IL-18 was decreased in hypertrophic scar tissues and fibroblasts compared to the normal skin tissues and fibroblasts, respectively. The decreased proliferation and increased apoptosis of hypertrophic scar fibroblasts were found after rhIL-18 treatment with the enhanced expressions of FasL, sFasL FADD, Caspase-8, Caspase-9 and Caspase-3 in a dose-dependent manner. The VAS and thickness of scars in rabbit ear was decreased as time went on after rhIL-18 treatment with the decreases in scar elevation index (SEI) and the increases in FasL expression. Conclusion IL-18 curbs the proliferation and promotes the apoptosis of hypertrophic scar fibroblasts via enhancing FasL expression, so it may be a potential target in treatment of hypertrophic scar.