AGEs and HMGB1 Increase Inflammatory Cytokine Production from Human Placental Cells, Resulting in an Enhancement of Monocyte Migration

作者：Shirasuna Koumei^*; Seno Kotomi; Ohtsu Ayaka; Shiratsuki Shogo; Ohkuchi Akihide; Suzuki Hirotada; Matsubara Shigeki; Nagayama Shiho; Iwata Hisataka; Kuwayama Takehito

来源：American Journal of Reproductive Immunology, 2016, 75(5): 557-568.

DOI：10.1111/aji.12506

• advanced glycation end products
• high-mobility group box-1
• inflammation
• placenta

ProblemAdvanced glycation end products (AGEs) and high-mobility group box-1 (HMGB1) are considered contributing to placental inflammation. We examined the effect of AGEs and HMGB1 on cytokines from Sw.71 human trophoblast cell lines and the interactions between Sw.71 cells and THP-1-monocytes.
Methods of studySw.71 cells were cultured with/without AGEs or HMGB1. We examined the role of AGEs or HMGB1 on THP1 migration and effect of AGEs on IL-6 from Sw.71 cells using co-cultures or conditioned medium from THP-1 cells.
ResultsAGEs and HMGB1 increased interleukin (IL)-6, IL-8, and chemokine C-C motif ligand 2 (CCL2) secretion from Sw.71 cells. The secretion of IL-6 was dependent on reactive oxygen species (ROS) and NF-B. AGEs stimulated IL-6 secretion through receptor RAGE and TLR4, whereas HMGB1 stimulated it through TLR4. AGEs, but not HMGB1, increased monocyte migration via IL-8 and CCL2 from Sw.71 cells. THP-1 monocytes induced IL-6 secretion from Sw.71 cells, and AGEs further stimulated it.
ConclusionsAGEs and HMGB1 may promote sterile placental inflammation cooperating with monocytes/macrophages.

• 出版日期2016-5