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

Abstract

PROBLEM:

Advanced 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 STUDY:

Sw.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.

RESULTS:

AGEs 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-κB. 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.

CONCLUSIONS:

AGEs and HMGB1 may promote sterile placental inflammation cooperating with monocytes/macrophages.

• Authors: Koumei Shirasuna, Kotomi Seno, Ayaka Ohtsu, Shogo Shiratsuki, Akihide Ohkuchi, Hirotada Suzuki, Shigeki Matsubara, Shiho Nagayama, Hisataka Iwata, Takehito Kuwayama
• Journal: American journal of reproductive immunology (New York, N.Y. : 1989) (Am J Reprod Immunol) Vol. 75 Issue 5 Pg. 557-68 (May 2016) ISSN: 1600-0897 [Electronic] Denmark
• PMID: 26961863 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Chemical References

• Chemokine CCL2
• Glycation End Products, Advanced
• HMGB1 Protein
• HMGB1 protein, human
• Inflammation Mediators
• Interleukin-6
• Interleukin-8
• Reactive Oxygen Species
• TLR4 protein, human
• Toll-Like Receptor 4

Topics

• Cell Communication
• Cell Line
• Cell Movement
• Chemokine CCL2 (metabolism)
• Coculture Techniques
• Female
• Glycation End Products, Advanced (immunology)
• HMGB1 Protein (immunology)
• Humans
• Inflammation (immunology)
• Inflammation Mediators (metabolism)
• Interleukin-6 (metabolism)
• Interleukin-8 (metabolism)
• Monocytes (physiology)
• Pregnancy (immunology)
• Reactive Oxygen Species (metabolism)
• Toll-Like Receptor 4 (metabolism)
• Trophoblasts (immunology)