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Interleukin 10 prevents apoptosis of brain endothelium during bacteremia
Author(s) -
Londono Diana,
Diego Cadavid
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.136.8
Subject(s) - downregulation and upregulation , apoptosis , endothelial stem cell , immunology , biology , lipoprotein , fas ligand , endothelium , tumor necrosis factor alpha , microbiology and biotechnology , programmed cell death , endocrinology , biochemistry , cholesterol , gene , in vitro
IL‐10 deficient mice infected with the relapsing fever bacterium Borrelia turicatae rapidly succumb to brain hemorrhage if they are unable to clear peak bacteremia. Here we investigated the protective role of IL‐10 during relapsing‐remitting bacterial infection and explored the molecular events involved in protection of brain endothelium by IL‐10. The results showed that severe endothelial cell injury leading to hemorrhage in the brain and other organs occurred in IL‐10 deficient mice during relapsing‐remitting infection. Human brain microvascular endothelial cells (HBMEC) upon exposure to whole bacteria or purified bacterial lipoprotein are rapidly killed by apoptosis and produced abundant pro‐inflammatory mediators but did not produce any IL‐10. HBMEC apoptosis during exposure to low number of bacteria was associated with down regulation of TNF and TNFAIP3 and upregulation of BAX. In contrast, exposure to high concentrations of purified outer membrane lipoprotein was associated with dramatic upregulation of FAS, FAS ligand, and the adaptor molecules RIPK1 and CFLAR. Exogenous IL‐10 reversed all the apoptotic signaling changes induced by whole bacteria or purified lipoprotein. The results indicate that IL‐10 prevent brain endothelial cell injury and point to a prominent role for bacterial lipoprotein mediated activation of different apoptosis pathways in this process.