Comprehensive analysis of the transcriptional response of human decidual cells to lipopolysaccharide stimulation

Abstract

Decidual cells are central to innate immunity at the maternal/fetal interface. We sought to characterize the response of decidual cells to stimulation and then removal of lipopolysaccharide (LPS) using a whole genome approach. Decidual cells were isolated from term unlabored cesarean sections. Cells were stimulated with LPS and RNA isolated both prestimulation and 2 and 24 h post-stimulation. Media were changed and RNA extracted 48 h later. Gene expression was measured using Agilent 44K whole genome microarrays. Data were visualized and interpreted using Ingenuity Pathway Analysis (IPA) software and selected (n = 5) target gene expression was verified with quantitative real-time PCR. Genes related to immune function were up-regulated at 2 and 24 h after LPS exposure and then generally returned to baseline or were at least substantially reduced after LPS removal. Pathway analysis also revealed that genes involved in lipid metabolism (specifically cholesterol and steroid biosynthesis), iron metabolism, and the plasminogen system were coordinately altered following exposure to LPS. Our novel, preliminary findings provide insight into possible mechanisms via which the host inflammatory response could contribute to preterm birth and warrant further investigation in preterm samples.

Decidual stromal cell‐derived PGE2 regulates macrophage responses to microbial threat

“…[58][59][60][61] The dTHESC cells did not demonstrate significantly increased production of CCL5, IL-10, TGFβ 1, MIC-1, G-CSF, or IL-1β following LPS exposure. Prior studies have reported mixed results in TNFα production in response to LPS by decidual stromal cells, 58,62,63 and VEGF was below the limit of detection in our system. In our studies, PMA-differentiated THP-1 macrophage-like cells produced significant increases in TNFα in response to LPS.…”

Current concepts in maternal-fetal immunology: Recognition and response to microbial pathogens by decidual stromal cells

“…With regards to additional transcriptional effects, studies using primary human DSCs have illustrated that LPS increases the expression of a number of genes in the NF-κB pathway, including monocyte chemoattractant protein-1 (MCP-1) [31], IL-1β [31, 32], colony stimulating factor-2 (CSF-2) [31] and IL-8 [16, 31]. Other studies utilizing primary human DSCs observed increased gene expression of TNF-α [32, 33], IL-6 [17, 32, 33], lipid metabolism genes ( e.g. , those involved in prostaglandin production) [32], and decreased solute carrier family 40 member 1 (SLC40A1), which is key in modulating iron levels [32].…”

“…Other studies utilizing primary human DSCs observed increased gene expression of TNF-α [32, 33], IL-6 [17, 32, 33], lipid metabolism genes ( e.g. , those involved in prostaglandin production) [32], and decreased solute carrier family 40 member 1 (SLC40A1), which is key in modulating iron levels [32]. Utilizing an immortalized line of human decidualized endometrial stromal cells, Grasso and colleagues assessed responses to LPS, which also elicited increased gene expression of regulated on activation, normal T cell expressed and secreted (RANTES), MCP-1 and IL-8 [34].…”

“…With regard to additional transcriptional effects, studies using primary human DSCs have illustrated that LPS increases the expression of a number of genes in the NF-κB pathway, including monocyte chemo-attractant protein-1 (MCP-1),31 IL-1β,31,32 colony-stimulating factor-2 (CSF-2),31 and IL-8 16,31. Other studies utilizing primary human DSCs observed increased gene expression of TNFα, 32,33 IL-6, 17,32,33 lipid metabolism genes (eg, those involved in prostaglandin production),32 and decreased solute carrier family 40 member 1 (SLC40A1), which is key in modulating iron levels 32. Utilizing an immortalized line of human decidualized endometrial stromal cells, Grasso and colleagues assessed responses to LPS, which also elicited the increased gene expression of regulated on activation, normal T cell expressed and secreted (RANTES), MCP-1, and IL-8 34.…”

Transcriptome, Spliceosome and Editome Expression Patterns of the Porcine Endometrium in Response to a Single Subclinical Dose of Salmonella Enteritidis Lipopolysaccharide

“…Research into human decidual cells has demonstrated that LPS influences the expression of genes engaged in lipid metabolism, including cholesterol and steroid biosynthesis [62]. Proprotein convertase subtilisin/kexin type 9 (product of PCSK9), the key regulator of serum cholesterol levels, inhibits LPS removal from the bloodstream [63].…”