Carbon monoxide prevents apoptosis induced by uropathogenic Escherichia coli toxins.
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.
Chen
Ming
M
Department of Clinical Science, Division of Pediatrics, Karolinska Institutet, Stockholm, Sweden. Ming.Chen@ki.se
Tofighi
Roshan
R
Bao
Wenjie
W
Aspevall
Olle
O
Jahnukainen
Timo
T
Gustafsson
Lars E
LE
Ceccatelli
Sandra
S
Celsi
Gianni
G
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001427:Bacterial Toxins / Q000378:metabolism*; D002248:Carbon Monoxide / Q000494:pharmacology*; D002648:Child; D004926:Escherichia coli / Q000378:metabolism*; D004927:Escherichia coli Infections / Q000382:microbiology*; D051547:Heme Oxygenase-1 / Q000378:metabolism; D006460:Hemolysin Proteins / Q000494:pharmacology; D006801:Humans; D007687:Kidney Tubules, Proximal / Q000382:microbiology / Q000473:pathology*; D018374:LLC-PK1 Cells; D011704:Pyelonephritis / Q000382:microbiology* / Q000473:pathology; D051381:Rats; D013552:Swine; D015854:Up-Regulation
D001427:Bacterial Toxins; D006460:Hemolysin Proteins; D002248:Carbon Monoxide; D051547:Heme Oxygenase-1