- 作者: Naotoshi Sugimoto, Hue Leu, Natsumi Inoue, Masaki Shimizu, Tomoko Toma, Mondo Kuroda, Takekatsu Saito, Taizo Wada , Akihiro Yachie
- 作者服務機構: Department of Physiology, Graduate School of Medical Science, Kanazawa University, Takara-machi, Kanazawa , Japan
- 中文摘要: --
- 英文摘要:
Background:
In 2011, there was an outbreak of Shiga toxin-producing Escherichia coli (STEC) infections in Japan. Approximately 62 % of patients with hemolytic-uremic syndrome also showed symptoms of encephalopathy. To determine the mechanisms of onset for encephalopathy during STEC infections, we conducted an in vitro study with glial cell lines and primary glial cells.
Results:
Shiga toxin 2 (Stx-2) in combination with lipopolysaccharide (LPS), or LPS alone activates nuclear factor-κB (NF-κB) signaling in glial cells. Similarly, Stx-2 in combination with LPS, or LPS alone increases expression levels of aquaporin 4 (AQP4) in glial cells. It is possible that overexpression of AQP4 results in a rapid and increased influx of osmotic water across the plasma membrane into cells, thereby inducing cell swelling and cerebral edema.
Conclusions:
We have showed that a combination of Stx-2 and LPS induced apoptosis of glial cells recently. Glial cells are indispensable for cerebral homeostasis; therefore, their dysfunction and death impairs cerebral homeostasis and results in encephalopathy. We postulate that the onset of encephalopathy in STEC infections occurs when Stx-2 attacks vascular endothelial cells of the blood–brain barrier, inducing their death. Stx-2 and LPS then attack the exposed glial cells that are no longer in contact with the endothelial cells. AQP4 is overexpressed in glial cells, resulting in their swelling and adversely affecting cerebral homeostasis. Once cerebral homeostasis is affected in such a way, encephalopathy is the likely result in STEC patients.
- 中文關鍵字: --
- 英文關鍵字: Encephalopathy; Aquaporin 4 (AQP4); Lipopolysaccharide (LPS); Shiga toxin (Stx); Nuclear factor-κB (NF-κB) signaling