Tumor necrosis factor-α modifies the effects of Shiga toxin on glial cells.
Shiga toxin (STX) is one of the main factors inducing hemorrhagic colitis and hemolytic-uremic syndrome (HUS) in infections with STX-producing Escherichia coli (STEC). Approximately 62% of patients with HUS showed symptoms of encephalopathy in the 2011 Japanese outbreak of STEC infections. At that time, we reported elevated serum concentrations of tumor necrosis factor (TNF)-α in patients with acute encephalopathy during the HUS phase. In the current study, we investigated whether TNF-α augments the effects of STX in glial cell lines and primary glial cells. We found that TNF-α alone or STX in combination with TNF-α activates nuclear factor-κB (NF-κB) signaling and inhibits growth of glial cells. The magnitude of the NF-κB activation and the inhibition of cell growth by the STX and TNF-α combination was greater than that obtained with TNF-α alone or STX alone. Thus, this in vitro study reveals the role of TNF-α in glial cells during STEC infections.
Department of Pediatrics, Graduate School of Medical Science, Kanazawa University, Kanazawa, Japan; Dan Phuong General Hospital, Hanoi, Vietnam. Electronic address: nevergiveup.hue@gmail.com.
Hue
H
Leu
Department of Pediatrics, Graduate School of Medical Science, Kanazawa University, Kanazawa, Japan; Department of Physiology, Graduate School of Medical Science, Kanazawa University, Kanazawa, Japan. Electronic address: ns@med.kanazawa-u.ac.jp.
Naotoshi
N
Sugimoto
Department of Pediatrics, Graduate School of Medical Science, Kanazawa University, Kanazawa, Japan. Electronic address: shimizum@staff.kanazawa-u.ac.jp.
Masaki
M
Shimizu
Department of Pediatrics, Graduate School of Medical Science, Kanazawa University, Kanazawa, Japan. Electronic address: tomoko-t@staff.kanazawa-u.ac.jp.
Tomoko
T
Toma
Department of Pediatrics, Graduate School of Medical Science, Kanazawa University, Kanazawa, Japan. Electronic address: taizo@staff.kanazawa-u.ac.jp.
Taizo
T
Wada
Department of Pediatrics, Graduate School of Medical Science, Kanazawa University, Kanazawa, Japan. Electronic address: kohta@staff.kanazawa-u.ac.jp.
Kunio
K
Ohta
Department of Pediatrics, Graduate School of Medical Science, Kanazawa University, Kanazawa, Japan. Electronic address: yachie@staff.kanazawa-u.ac.jp.
Akihiro
A
Yachie
D000818:Animals; D001927:Brain Diseases / Q000276:immunology*; D002460:Cell Line; D049109:Cell Proliferation; D054307:Enterotoxigenic Escherichia coli / Q000276:immunology*; D004927:Escherichia coli Infections / Q000276:immunology*; D006801:Humans; D016328:NF-kappa B / Q000378:metabolism; D009457:Neuroglia / Q000276:immunology*; D051381:Rats; D022621:Shiga Toxin / Q000276:immunology / Q000378:metabolism*; D015398:Signal Transduction; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000378:metabolism*
D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D022621:Shiga Toxin
Encephalopathy; Nuclear factor-κB; Outbreak; Shiga toxin