Original Article

Pediatric Nephrology

, Volume 21, Issue 3, pp 382-389

First online:

Carbon monoxide prevents apoptosis induced by uropathogenic Escherichia coli toxins

  • Ming ChenAffiliated withDepartment of Clinical Science, Division of Pediatrics, Karolinska InstitutetDepartment of Medical Nutrition NOVUM, Karolinska University Hospital-Huddinge Email author 
  • , Roshan TofighiAffiliated withDivision of Toxicology and Neurotoxicology, Department of Environmental Medicine, Karolinska Institute
  • , Wenjie BaoAffiliated withMicrobiology and Tumor Biology Center, Karolinska Institute
  • , Olle AspevallAffiliated withDepartment of Clinical Bacteriology, Karolinska Institute
  • , Timo JahnukainenAffiliated withDepartment of Pediatrics, Turku University Hospital
  • , Lars E. GustafssonAffiliated withDepartment of Physiology and Pharmacology, Karolinska Institute
  • , Sandra CeccatelliAffiliated withDivision of Toxicology and Neurotoxicology, Department of Environmental Medicine, Karolinska Institute
  • , Gianni CelsiAffiliated withDepartment of Clinical Science, Division of Pediatrics, Karolinska Institutet

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Abstract

Urinary tract infections (UTIs) are often caused by Escherichia coli (E. coli). Previous studies have demonstrated that up-regulation of heme oxygenase-1 (HO-1) may trigger a survival mechanism against renal cell death induced by E. coli toxins. The present study analyses the role of carbon monoxide (CO), an end product of HO-1, in the survival mechanism. Moreover, we identified hemolysin as a putative pro-apoptotic toxin in the E. coli supernatant. Tubular cells were incubated with CO in the presence or absence of E. coli toxins. Uropathogenic or transformants of non-pathogenic strains expressing hemolysin were used. We found that the survival pathway during E. coli infection might be activated by HO-1-derived production of CO. The protection by CO was also associated with up-regulation of p21 protein expression. Furthermore, we found that in children with pyelonephritis, all the E. coli strains expressing hemolysin induced apoptosis. In E. coli strains not expressing hemolysin, only 45% of the strains could induce apoptosis. In conclusion, generation of CO elicited by HO-1 could promote survival signaling in renal cells. Hemolysin is one of the secreted toxins that are involved in inducing apoptosis during UTI.

Keywords

Carbon monoxide Cell death Hemolysin Heme oxygenase-1 Nitric oxide Pyelonephritogenic E. coli