Jung Mechthild, Sabat Robert, Krätzschmar Jörn, Seidel Henrik, Wolk Kerstin, Schönbein Christiane, Schütt Sabine, Friedrich Markus, Döcke Wolf-Dietrich, Asadullah Khusru, Volk Hans-Dieter, Grütz Gerald
Institute of Medical Immunology, Charité, Humboldt-University Berlin, Berlin, Germany.
Eur J Immunol. 2004 Feb;34(2):481-93. doi: 10.1002/eji.200324323.
Interleukin-10 (IL-10), originally identified as an inhibitor of pro-inflammatory cytokine production, exerts multiple immunomodulatory functions. Its ability to inhibit a Th1 response has been used in clinical trials for the treatment of inflammatory diseases including psoriasis. However, little is known about the molecular mechanisms of IL-10 functions. We aimed at identifying possible mediators of in vitro IL-10 treatment in monocytes by gene chip technology using Hu95a Affymetrix mRNA arrays with 12,000 genes. To prove relevance of the identified genes for the clinical situation we compared these in vitro results with genes being regulated by IL-10 in peripheral blood mononuclear cells from psoriatic patients undergoing IL-10 therapy. A high proportion of the 1,600 genes up-regulated and 1,300 genes down-regulated in vitro was found to be similarly regulated in vivo. Some genes, which were previously unknown to be regulated by IL-10, can be assigned to known IL-10 functions like e.g. the increase of pathogen clearance. Other new potentially immunomodulating genes have been identified to be regulated by IL-10, but their impact needs to be experimentally evaluated. We could confirm a recently reported up-regulation of heme oxygenase-1 (HO-1). However, we demonstrate that the anti-inflammatory mechanisms of IL-10 remain functional even when HO-1 is irreversibly inhibited.
白细胞介素-10（IL-10）最初被鉴定为促炎细胞因子产生的抑制剂，具有多种免疫调节功能。其抑制Th1反应的能力已在包括银屑病在内的炎症性疾病治疗的临床试验中得到应用。然而，关于IL-10功能的分子机制知之甚少。我们旨在通过使用具有12000个基因的Hu95a Affymetrix mRNA芯片技术，鉴定单核细胞体外IL-10治疗的可能介质。为了证明所鉴定基因与临床情况的相关性，我们将这些体外结果与接受IL-10治疗的银屑病患者外周血单核细胞中受IL-10调控的基因进行了比较。发现体外上调的1600个基因和下调的1300个基因中有很大一部分在体内受到类似的调控。一些以前未知受IL-10调控的基因可归因于已知的IL-10功能，如病原体清除的增加。已鉴定出其他新的潜在免疫调节基因受IL-10调控，但其影响需要通过实验进行评估。我们可以证实最近报道的血红素加氧酶-1（HO-1）的上调。然而，我们证明即使HO-1被不可逆地抑制，IL-10的抗炎机制仍然有效。
