Interleukin-33/ST2 signaling contributes to the severity of hemolytic uremic syndrome induced by enterohemorrhagic Escherichia coli

Autor: Natsumi Inoue, Shimpei Yamada, Akihiro Yachie, Mondo Kuroda, Masaki Shimizu, Naotoshi Sugimoto
Rok vydání: 2018
Předmět:
Male
Physiology
030232 urology & nephrology
030204 cardiovascular system & hematology
urologic and male genital diseases
Severity of Illness Index
Shiga Toxin 2
Umbilical vein
Pathogenesis
0302 clinical medicine
hemic and lymphatic diseases
Medicine
Child
Cells
Cultured
Escherichia coli Infections
biology
Interleukin
Shiga toxin
Nephrology
Receptors
Tumor Necrosis Factor
Type I
Child
Preschool
Enterohemorrhagic Escherichia coli
Female
medicine.symptom
Signal Transduction
Adult
medicine.medical_specialty
Adolescent
Encephalopathy
Inflammation
Proinflammatory cytokine
03 medical and health sciences
Young Adult
Physiology (medical)
Internal medicine
Human Umbilical Vein Endothelial Cells
Humans
Receptors
Tumor Necrosis Factor
Type II
business.industry
Interleukin-6
Infant
medicine.disease
Interleukin-33
Interleukin-1 Receptor-Like 1 Protein
Interleukin 33
ROC Curve
Case-Control Studies
Immunology
Hemolytic-Uremic Syndrome
biology.protein
business
Zdroj: Clinical and experimental nephrology. 23(4)
ISSN: 1437-7799
Popis: Interleukin (IL)-33 plays an important role in host defense, immune regulation, and inflammation. This study assessed IL-33’s role in the pathogenesis of severe hemolytic uremic syndrome (HUS) induced by enterohemorrhagic Escherichia coli (EHEC). We also investigated the clinical significance of IL-33 and soluble ST2 (soluble form of IL-33 receptor) serum levels in patients with EHEC-induced HUS. The role of IL-33 in Shiga toxin (STx)-2-induced endothelial injury was studied in human umbilical vein endothelial cells (HUVECs) in vitro. Blood samples were obtained from 21 HUS patients and 15 healthy controls (HC). The IL-33 and sST2 serum levels were quantified using an enzyme-linked immunosorbent assay. The results were compared to HUS’ clinical features. Cytotoxic assays indicated that IL-33 enhanced STx2 toxicity in HUVECs. Serum IL-33 levels in most HUS patients were below the lowest detection limit. On the other hand, serum sST2 levels in patients during the HUS phase were significantly higher than those in HC and showed a correlation with disease severity. Serum sST2 levels in patients with encephalopathy were significantly higher than those in patients without it. A serum sST2 level > 63.2 pg/mL was associated with a high risk of encephalopathy. Serum sST2 levels significantly correlated with serum levels of inflammatory cytokines related to the development of HUS. Our results indicate that IL-33 contributes to the severity of EHEC-induced HUS. Serum sST2 level in HUS patients correlated with disease activity, which suggests its potential role as a marker for disease activity and development of encephalopathy in patients with EHEC-induced HUS.
Databáze: OpenAIRE
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