Matsushita Mariko, Yamamoto Toshiyuki, Nishioka Kiyoshi
Department of Dermatology, Tokyo Medical and Dental University, School of Medicine, 1-5-45 Yushima, Bunkyo-ku, Tokyo, Japan.
Int Arch Allergy Immunol. 2004 Dec;135(4):348-56. doi: 10.1159/000082331. Epub 2004 Nov 24.
Interleukin-13 (IL-13) has been implicated in the pathogenesis of fibrotic conditions. Previously, a murine model for scleroderma has been established by repeated local injections of bleomycin. This animal model enabled us to study local expression and production of IL-13 in skin lesions during disease progression.
Dermal sclerosis (DSc) was induced by repeated subcutaneous injections of bleomycin (1 mg/ml) in C3H/HeJ mice. IL-13 and IL-4 expressions were examined by RT-PCR, ELISA and immunohistochemistry.
RT-PCR showed that both IL-4 and IL-13 mRNA levels in skin lesions were increased and peaked after 4 weeks of bleomycin treatment. Quantification by densitometry revealed up to 4.2- and 1.9-fold increases, respectively. Immunohistochemical localization showed in skin lesions expression of IL-13 on infiltrating inflammatory cells, including mononuclear cells and possibly mast cells, increased with DSc progression. IL-13 protein production was also significantly increased. In skin lesions, IL-13 receptor (IL-13R) alpha2 expression was augmented mainly in the infiltrating mononuclear cells after 4 weeks of bleomycin exposure. IL-13Ralpha2, but not IL-13Ralpha1, mRNA was upregulated in the whole skin after 4 weeks. On the contrary, mRNA expression of IL-13Ralpha1 and IL- 13Ralpha2 was significantly altered in the cultured fibroblasts derived from bleomycin-treated skin.
These data demonstrate that in skin lesions levels of IL-13 as well as its receptor increase in parallel with DSc progression, suggesting that IL-13 promotes the progression of cutaneous fibrosis/sclerosis in the murine model of bleomycin-induced scleroderma.
白细胞介素-13（IL-13）与纤维化疾病的发病机制有关。此前，通过反复局部注射博来霉素建立了硬皮病的小鼠模型。该动物模型使我们能够研究疾病进展过程中皮肤病变中IL-13的局部表达和产生情况。
在C3H/HeJ小鼠中通过反复皮下注射博来霉素（1 mg/ml）诱导皮肤硬化（DSc）。通过逆转录聚合酶链反应（RT-PCR）、酶联免疫吸附测定（ELISA）和免疫组织化学检测IL-13和IL-4的表达。
RT-PCR显示，皮肤病变中IL-4和IL-13的mRNA水平均升高，并在博来霉素治疗4周后达到峰值。通过光密度测定法定量显示分别增加了4.2倍和1.9倍。免疫组织化学定位显示，在皮肤病变中，IL-13在浸润性炎症细胞（包括单核细胞以及可能的肥大细胞）上的表达随着DSc进展而增加。IL-13蛋白的产生也显著增加。在皮肤病变中，博来霉素暴露4周后，IL-13受体（IL-13R）α2的表达主要在浸润的单核细胞中增强。4周后，整个皮肤中IL-13Rα2而非IL-13Rα1的mRNA上调。相反，来自博来霉素处理皮肤的培养成纤维细胞中IL-13Rα1和IL-13Rα2的mRNA表达发生显著改变。
这些数据表明，在皮肤病变中，IL-13及其受体水平与DSc进展平行增加，提示IL-13在博来霉素诱导的硬皮病小鼠模型中促进皮肤纤维化/硬化的进展。
