Protection against TGF-β1-induced fibrosis effects of IL-10 on dermal fibroblasts and its potential therapeutics for the reduction of skin scarring

• DOI: 10.1007/s00403-013-1314-0
• Publication Date: 2013-01-15T08:44:32Z
• Authors: Ji-Hong Shi; Hao Guan; Shan Shi; Wei-Xia Cai; Xiao-Zhi Bai; Xiao-Long Hu; Xiao-Bin Fang; Jia-Qi Liu; Ke Tao; Xiong-Xiang Zhu; Chao-Wu Tang; Da-Hai Hu
• Keywords: Mice, Inbred BALB C; Wound Healing; 0303 health sciences; Dermis; Fibroblasts; In Vitro Techniques; Fibrosis; Actins; Collagen Type I; Interleukin-10; 3. Good health; Transforming Growth Factor beta1; Cicatrix; Disease Models, Animal; Mice; 03 medical and health sciences; Collagen Type III; Matrix Metalloproteinase 8; Animals; Humans; Matrix Metalloproteinase 1; Cells, Cultured

Scarring, tightly associated with fibrosis, is a significant symptomatic clinical problem. Interleukin 10 (IL-10) has been identified as a candidate scar-improving therapy based on preclinical studies. However, the molecular mechanism of IL-10 in scar improvement is still uncertain. In this study, human dermal fibroblasts stimulated with TGF-β1 were treated with IL-10 to analyze the mRNA and some of proteins' expression levels of type I collagen (Col1), type III collagen (Col3), alpha-smooth muscle actin (α-SMA), matrix metalloproteinase-1 (MMP1), MMP2, MMP8 and tissue inhibitor of metalloproteinase 1 (TIMP1), TIMP2 by real-time PCR and Western blot, to observe α-SMA-positive fibroblasts by immunocytochemistry. The contracture and improvement of fibroblast-populated collagen lattice (FPCL) and a murine model of wound healing were used to evaluate the scar-improving effects by histological staining. The results showed that IL-10 can significantly down-regulate the mRNA and protein expression levels of Col1, Col3, α-SMA, and up-regulate the mRNA expression levels of MMP1 and MMP8, and decrease α-SMA-positive fibroblasts. FPCL analysis showed that the IL-10 (20 ng/ml) can significantly inhibit the contracture, improve the architecture of FPCL. Wounds injected with IL-10 demonstrated that the appearance of scar was improved, the wound margin of scarring was narrow, and the deposition of collagens (Col1 and Col3) in regenerated tissue was relieved. These results provide direct evidences that IL-10 has the inhibitory effects on the excessive deposition of extracellular matrix components and fibroblast-to-myofibroblast transition, and show that IL-10 has the potential therapy in prevention and reduction of skin scarring.