Reitamo S, Remitz A, Tamai K, Ledo I, Uitto J
Department of Dermatology, Jefferson Medical College, Thomas Jefferson University, Philadelphia, PA 19107.
Biochem J. 1994 Sep 1;302 ( Pt 2)(Pt 2):331-3. doi: 10.1042/bj3020331.
In immune cells, such as T cells and monocytes, interleukin 10 (IL-10) has regulatory functions on a number of cytokines, including IL-1, IL-2, IL-8 and tumour necrosis factor-alpha expression. However, the effects of IL-10 have not previously been studied in detail in connective-tissue cells. In the present study, we show that recombinant human IL-10 at physiological concentrations has direct effects on the expression of the human elastin gene both in vivo and in vitro. Transgenic mice expressing a human elastin promoter/chloramphenicol acetyltransferase (CAT) reporter gene construct were injected subcutaneously with IL-10 (1-100 ng) and the site of injection was biopsied after 24 h. CAT assay revealed an increase of up to 3.5-fold in the promoter activity with 10 ng of IL-10. Transforming growth factor-beta 2 (TGF-beta 2) is known to up-regulate elastin gene expression in cultured fibroblasts. When IL-10 was added to such cultures, the effects of TGF-beta 2 on elastin mRNA levels were synergistically potentiated. These results suggest that IL-10 has an up-regulatory effect on elastin gene expression.
在免疫细胞,如T细胞和单核细胞中,白细胞介素10(IL-10)对多种细胞因子具有调节功能,包括白细胞介素1、白细胞介素2、白细胞介素8和肿瘤坏死因子-α的表达。然而,此前尚未在结缔组织细胞中详细研究过IL-10的作用。在本研究中,我们发现生理浓度的重组人IL-10在体内和体外均对人弹性蛋白基因的表达有直接影响。将表达人弹性蛋白启动子/氯霉素乙酰转移酶(CAT)报告基因构建体的转基因小鼠皮下注射IL-10(1 - 100 ng),24小时后对注射部位进行活检。CAT分析显示,注射10 ng IL-10后启动子活性增加高达3.5倍。已知转化生长因子-β2(TGF-β2)可上调培养的成纤维细胞中弹性蛋白基因的表达。当将IL-10添加到此类培养物中时,TGF-β2对弹性蛋白mRNA水平的影响会协同增强。这些结果表明IL-10对弹性蛋白基因表达具有上调作用。