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

Marco Rossi, Andrew M. Sharkey, Paola Viganò, Giovina Fiore, Rob Furlong, Pasquale Florio, Guido Ambrosini, Stephen K. Smith, Felice Petraglia

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Abstract

Interleukin-1β (IL-1β) 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-1β 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-1β 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-1β. 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, extracellular matrix (ECM) remodelling and cell cycle regulation. Genes which were regulated by IL-1β 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-1β, which are involved in leukocyte recruitment, ECM remodelling and other cellular functions. Changes in three genes, IL-8, colony-stimulating factor 2 and aldo-keto reductase family 1 member 1, which were upregulated by IL-1β, were verified using real-time PCR. Novel functions regulated by IL-1β 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-1β in disorders of the endometrium, especially in implantation-related infertility and endometriosis, in which this cytokine plays a major role.

Original languageEnglish
Pages (from-to)721-729
Number of pages9
JournalReproduction
Volume130
Issue number5
DOIs
Publication statusPublished - Nov 2005

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ASJC Scopus subject areas

  • Obstetrics and Gynaecology
  • Cell Biology
  • Endocrinology
  • Embryology

Cite this

Rossi, M., Sharkey, A. M., Viganò, P., Fiore, G., Furlong, R., Florio, P., Ambrosini, G., Smith, S. K., & Petraglia, F. (2005). Identification of genes regulated by interleukin-1β in human endometrial stromal cells. Reproduction, 130(5), 721-729. https://doi.org/10.1530/rep.1.00688