Rossi Marco, Sharkey Andrew M, Viganò Paola, Fiore Giovina, Furlong Rob, Florio Pasquale, Ambrosini Guido, Smith Stephen K, Petraglia Felice
Obstetrics and Gynaecology, Department of Paediatrics, Obstetrics and Reproductive Medicine, University of Siena, Italy.
Reproduction. 2005 Nov;130(5):721-9. doi: 10.1530/rep.1.00688.
Interleukin-1beta (IL-1b) is an important immune regulatory factor that in human endometrium plays a role in both menstruation and implantation in the event of pregnancy. It promotes inflammatory-like processes and also stimulates tissue remodelling. We present a cDNA microarray study documenting the major effects of IL-1beta on gene expression in stromal cells from human endometrium. Endometrial stromal cells from five normal healthy women at the mid secretory phase were cultured with or without IL-1beta at 50 and 500 pg/ml for 48 h. cDNA microarrays were used to compare the levels of gene expression in total RNA isolated from cells stimulated with IL-1beta. These cDNA arrays were produced containing 15 164 sequence-verified clones, which included genes known to be important in angiogenesis, immune modulators, apoptosis, cell signalling, extra-cellular matrix (ECM) remodelling and cell cycle regulation. Genes which were regulated by IL-1beta were identified by analysis of the microarray data using the Significance Analysis of Microarrays software package. Upregulated (n = 23) and downregulated (n = 6) different genes were observed, which changed at least 3-fold, at a false discovery rate of less than 2% (P < 0.02). Our results have identified genes regulated by IL-1beta, which are involved in leukocyte recruitment, ECM remodelling and other cellular functions. Changes in three genes, IL-8, colony-stimulating factor 2 and aldoketo reductase family 1 member 1, which were upregulated by IL-1beta, were verified using real-time PCR. Novel functions regulated by IL-1beta in endometrium, including genes involved in free radical protection, and fatty acid metabolism were also identified. These results also provide new insights into the role of IL-1beta in disorders of the endometrium, especially in implantation-related infertility and endometriosis, in which this cytokine plays a major role.
白细胞介素-1β（IL-1β）是一种重要的免疫调节因子，在人类子宫内膜中，它在月经以及怀孕时的着床过程中均发挥作用。它促进类似炎症的过程，还刺激组织重塑。我们开展了一项cDNA微阵列研究，记录IL-1β对人子宫内膜基质细胞基因表达的主要影响。来自五名处于分泌中期的正常健康女性的子宫内膜基质细胞，分别在添加或不添加50和500 pg/ml IL-1β的情况下培养48小时。使用cDNA微阵列比较从经IL-1β刺激的细胞中分离出的总RNA中的基因表达水平。这些cDNA阵列包含15164个经序列验证的克隆，其中包括已知在血管生成、免疫调节、细胞凋亡、细胞信号传导、细胞外基质（ECM）重塑和细胞周期调控中起重要作用的基因。使用微阵列数据分析软件包对微阵列数据进行分析，从而鉴定出受IL-1β调控的基因。观察到上调（n = 23）和下调（n = 6）的不同基因，其变化至少为3倍，错误发现率小于2%（P < 0.02）。我们的研究结果确定了受IL-1β调控的基因，这些基因参与白细胞募集、ECM重塑和其他细胞功能。使用实时PCR验证了IL-1β上调的三个基因（IL-8、集落刺激因子2和醛糖酮还原酶家族1成员1）的变化。还鉴定出IL-1β在子宫内膜中调控的新功能，包括参与自由基保护和脂肪酸代谢的基因。这些结果也为IL-1β在子宫内膜疾病中的作用提供了新的见解，尤其是在与着床相关的不孕症和子宫内膜异位症中，这种细胞因子起主要作用。
