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Caspase‐3‐dependent apoptosis in Escherichia coli ‐infected urothelium: involvement of inducible nitric oxide synthase
Author(s) -
ANDERSSON MARIA,
POLJAKOVIC MIRJANA,
PERSSON KATARINA
Publication year - 2006
Publication title -
bju international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.773
H-Index - 148
eISSN - 1464-410X
pISSN - 1464-4096
DOI - 10.1111/j.1464-410x.2006.06151.x
Subject(s) - nitric oxide synthase , apoptosis , urothelium , caspase 3 , biology , caspase , nitric oxide , peroxynitrite , microbiology and biotechnology , programmed cell death , superoxide , enzyme , endocrinology , biochemistry , urinary system
OBJECTIVE To investigate if nitric oxide (NO) derived from inducible NO synthase (iNOS) regulates apoptosis and/or cell shedding in uroepithelial cells in vivo and in vitro , as bladder epithelial cells undergo shedding during urinary tract infection, which is considered a part of the host’s defence and is thought to take place via an apoptotic pathway. MATERIALS AND METHODS Bladders and kidneys of mice infected with Escherichia coli were used to study caspase‐3 immunoreactivity at different times after infection. Wild‐type ( E. coli 1177) and type‐1 recombinant ( E. coli PKL4) bacteria were used. iNOS‐deficient mice were used to study the association of caspase‐3 with iNOS. Isolated human uroepithelial cells were used to examine the effect of the NO donor DETA/NO and the peroxynitrite generator SIN‐1 on caspase‐3 activity and cell shedding in vitro . RESULTS Many caspase‐3 immunoreactive neutrophils were found soon after infection and some superficial bladder epithelial cells were also immunoreactive for caspase‐3. Caspase‐3 immunoreactivity was also detected in neutrophils and bladder epithelial cells of infected iNOS‐deficient mice. There was no co‐expression between iNOS‐ and caspase‐3 in bladder epithelial cells. DETA/NO and SIN‐1 did not stimulate caspase‐3 activity or cell shedding in isolated human uroepithelial cells. CONCLUSIONS Caspase‐3 and iNOS are not co‐expressed in uroepithelial cells and apoptosis is evident in the absence of iNOS. Exogenous NO did not induce apoptosis or cell shedding in isolated human uroepithelial cells.