title: Protection against TGF-β1-induced fibrosis effects of IL-10 on dermal fibroblasts and its potential therapeutics for the reduction of skin scarring.
abstract: 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.
authors: Department of Burns and Cutaneous Surgery, Xijing Hospital, The Fourth Military Medical University, 17 Changle West Road, Xi'an 710032, Shaanxi, China.
authors: Ji-Hong
authors: JH
authors: Shi
authors: Hao
authors: H
authors: Guan
authors: Shan
authors: S
authors: Shi
authors: Wei-Xia
authors: WX
authors: Cai
authors: Xiao-Zhi
authors: XZ
authors: Bai
authors: Xiao-Long
authors: XL
authors: Hu
authors: Xiao-Bin
authors: XB
authors: Fang
authors: Jia-Qi
authors: JQ
authors: Liu
authors: Ke
authors: K
authors: Tao
authors: Xiong-Xiang
authors: XX
authors: Zhu
authors: Chao-Wu
authors: CW
authors: Tang
authors: Da-Hai
authors: DH
authors: Hu
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D002478:Cells, Cultured; D002921:Cicatrix / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control*; D024042:Collagen Type I / Q000378:metabolism; D024061:Collagen Type III / Q000378:metabolism; D020405:Dermis / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D004195:Disease Models, Animal; D005347:Fibroblasts / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology*; D005355:Fibrosis; D006801:Humans; D066298:In Vitro Techniques; D016753:Interleukin-10 / Q000494:pharmacology* / Q000627:therapeutic use*; D020781:Matrix Metalloproteinase 1 / Q000378:metabolism; D020784:Matrix Metalloproteinase 8 / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D053773:Transforming Growth Factor beta1 / Q000009:adverse effects* / Q000494:pharmacology; D014945:Wound Healing / Q000187:drug effects
chemical_list: C541116:ACTA2 protein, human; D000199:Actins; D024042:Collagen Type I; D024061:Collagen Type III; D053773:Transforming Growth Factor beta1; C544013:alpha-smooth muscle actin, mouse; D016753:Interleukin-10; D020784:Matrix Metalloproteinase 8; D020781:Matrix Metalloproteinase 1