Identification of genes regulated by interleukin-1 in human decidual cells: Elucidating mechanisms of infection-mediated preterm birth

Abstract

CELLS: ELUCIDATING MECHANISMS OF INFECTION-MEDIATED PRETERM BIRTH ASHLEY ROMAN, AMY STAGG, GREG DORSAINVILLE, PETER NATHANIELSZ, New York University, Obstetrics and Gynecology, New York, New York, University of Texas Health Science Center at San Antonio, Obstetrics and Gynecology, San Antonio, Texas OBJECTIVE: IL-1b is a cytokine produced by human decidua and macrophages in response to microbial invasion and has been linked to the multiple processes leading to preterm labor and delivery. To date, the effect of IL-1b on the decidual cell transcriptome has not been studied (based on a MEDLINE search using keywords ‘‘interleukin-1’’ and ‘‘pregnancy’’). The objective of this study is to characterize the pattern of gene expression in response to IL-1b in cultured decidual cells. STUDY DESIGN: Decidua was obtained from placentas of non-laboring patients at term cesarean delivery (N=6) and cultured using standard cell culture technique. Cultures were exposed to IL-1b or vehicle for 12 hours; total RNA was harvested and prepared for microarray study. The decidual transcriptome was studied using Affymetrix hgu133plus2.0 microarrays. Expression was normalized, the average probe intensity scaled, and a detection p-value used to predict gene expression. Fold-changes were calculated from mean signals in the IL-1b group versus controls; a 2-fold change was considered significant. Quantitative RT-PCR was performed for array confirmation. Groups were compared using Student t-test; significance at p!0.05. RESULTS: The expression of over 47,000 transcripts was evaluated. 208 transcripts were significantly up-regulated; 38 were significantly down-regulated. We confirmed the up-regulation of 6 genes (VEGF, VCAM-1, mPGES, GCSF, IL-6, and phospholipase A2) with RT-PCR (p!0.05 in all cases). Specific ontologic pathways activated by IL-1b were cytokine-cytokine receptor interaction, cell cycle, prostaglandin and leukotriene metabolism, glutamate metabolism, and phospholipid degradation. CONCLUSION: This first comprehensive assessment of the impact of IL-1b on gene expression in cultured decidual cells reveals significant differences in patterns of expression in multiple ontologic pathways. The genes and pathways identified may serve as potential therapeutic targets for preventing or arresting preterm labor.