Pediatric Nephrology

, Volume 21, Issue 3, pp 382–389

Carbon monoxide prevents apoptosis induced by uropathogenic Escherichia coli toxins

  • Ming Chen
  • Roshan Tofighi
  • Wenjie Bao
  • Olle Aspevall
  • Timo Jahnukainen
  • Lars E. Gustafsson
  • Sandra Ceccatelli
  • Gianni Celsi
Original Article


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.


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


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Copyright information

© IPNA 2005

Authors and Affiliations

  • Ming Chen
    • 1
    • 7
  • Roshan Tofighi
    • 2
  • Wenjie Bao
    • 3
  • Olle Aspevall
    • 4
  • Timo Jahnukainen
    • 5
  • Lars E. Gustafsson
    • 6
  • Sandra Ceccatelli
    • 2
  • Gianni Celsi
    • 1
  1. 1.Department of Clinical Science, Division of PediatricsKarolinska InstitutetStockholmSweden
  2. 2.Division of Toxicology and Neurotoxicology, Department of Environmental MedicineKarolinska InstituteStockholmSweden
  3. 3.Microbiology and Tumor Biology CenterKarolinska InstituteStockholmSweden
  4. 4.Department of Clinical BacteriologyKarolinska InstituteStockholmSweden
  5. 5.Department of PediatricsTurku University HospitalTurkuFinland
  6. 6.Department of Physiology and PharmacologyKarolinska InstituteStockholmSweden
  7. 7.Department of Medical Nutrition NOVUMKarolinska University Hospital-HuddingeStockholmSweden

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