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Carbon monoxide prevents apoptosis induced by uropathogenic Escherichia coli toxins

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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.

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Acknowledgements

This study was supported by the Swedish Research Council (Grants: 12963, 14727, 07919), Frimurare Foundation, Jerrings Foundation, Samariten Foundation and Ronald McDonald Barnfond.

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Authors and Affiliations

  1. Department of Clinical Science, Division of Pediatrics, Karolinska Institutet, Stockholm, Sweden

    Ming Chen & Gianni Celsi

  2. Division of Toxicology and Neurotoxicology, Department of Environmental Medicine, Karolinska Institute, Stockholm, Sweden

    Roshan Tofighi & Sandra Ceccatelli

  3. Microbiology and Tumor Biology Center, Karolinska Institute, Stockholm, Sweden

    Wenjie Bao

  4. Department of Clinical Bacteriology, Karolinska Institute, Stockholm, Sweden

    Olle Aspevall

  5. Department of Pediatrics, Turku University Hospital, Turku, Finland

    Timo Jahnukainen

  6. Department of Physiology and Pharmacology, Karolinska Institute, Stockholm, Sweden

    Lars E. Gustafsson

  7. Department of Medical Nutrition NOVUM, Karolinska University Hospital-Huddinge, 141 86 , Stockholm, Sweden

    Ming Chen

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  1. Ming Chen
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Correspondence to Ming Chen.

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Chen, M., Tofighi, R., Bao, W. et al. Carbon monoxide prevents apoptosis induced by uropathogenic Escherichia coli toxins. Pediatr Nephrol 21, 382–389 (2006). https://doi.org/10.1007/s00467-005-2140-1

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  • DOI: https://doi.org/10.1007/s00467-005-2140-1

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