Identification of genes regulated by interleukin-1β in human endometrial stromal cells

Marco Rossi, Andrew Sharkey, Andrew M Sharkey, Paola Viganò, Giovina Fiore, Rob Furlong, Pasquale Florio, Guido Ambrosini, S. K. Smith, Stephen K Smith, Felice Petraglia
Reproduction (Cambridge, England) · 2005 · vol. 130(5) , pp. 721–729 · doi:10.1530/rep.1.00688 · PMID:16264101 · W2050850257
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Abstract

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.

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Condition tags

endometriosisinfertility

MeSH descriptors

Endometrium Gene Expression Regulation Interleukin-1 Stromal Cells Aldehyde Reductase Aldehyde Reductase Cells, Cultured Endometrium Female Follicular Phase Follicular Phase Gene Expression Profiling Granulocyte-Macrophage Colony-Stimulating Factor Granulocyte-Macrophage Colony-Stimulating Factor Humans Interleukin-1 Interleukin-8 Interleukin-8 Oligonucleotide Array Sequence Analysis Pregnancy

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