| TRAIL limits excessive host immune responses in bacterial meningitis. | |
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MedLine Citation:
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PMID: 17571163 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Apart from potential roles in anti-tumor surveillance, the TNF-related apoptosis-inducing ligand (TRAIL) has important regulatory functions in the host immune response. We studied antiinflammatory effects of endogenous and recombinant TRAIL (rTRAIL) in experimental meningitis. Following intrathecal application of pneumococcal cell wall, a TLR2 ligand, we found prolonged inflammation, augmented clinical impairment, and increased apoptosis in the hippocampus of TRAIL(-/-) mice. Administration of rTRAIL into the subarachnoid space of TRAIL(-/-) mice or reconstitution of hematopoiesis with wild-type bone marrow cells reversed these effects, suggesting an autoregulatory role of TRAIL within the infiltrating leukocyte population. Importantly, intrathecal application of rTRAIL in wild-type mice with meningitis also decreased inflammation and apoptosis. Moreover, patients suffering from bacterial meningitis showed increased intrathecal synthesis of TRAIL. Our findings provide what we believe is the first evidence that TRAIL may act as a negative regulator of acute CNS inflammation. The ability of TRAIL to modify inflammatory responses and to reduce neuronal cell death in meningitis suggests that it may be used as a novel antiinflammatory agent in invasive infections. |
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Authors:
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Olaf Hoffmann; Josef Priller; Timour Prozorovski; Ulf Schulze-Topphoff; Nevena Baeva; Jan D Lunemann; Orhan Aktas; Cordula Mahrhofer; Sarah Stricker; Frauke Zipp; Joerg R Weber |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: The Journal of clinical investigation Volume: 117 ISSN: 0021-9738 ISO Abbreviation: J. Clin. Invest. Publication Date: 2007 Jul |
Date Detail:
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Created Date: 2007-07-03 Completed Date: 2007-09-18 Revised Date: 2009-11-18 |
Medline Journal Info:
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Nlm Unique ID: 7802877 Medline TA: J Clin Invest Country: United States |
Other Details:
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Languages: eng Pagination: 2004-13 Citation Subset: AIM; IM |
Affiliation:
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Department of Neurology, Laboratory of Molecular Psychiatry, Charité Universitätsmedizin Berlin, Berlin, Germany. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Antigens, CD18 / metabolism Cell Survival Cytokines / genetics Disease Models, Animal Gene Expression Regulation Genotype Gram-Positive Cocci / physiology Granulocytes / metabolism Hippocampus / immunology, metabolism, pathology Humans Leukocytes / cytology Male Meningitis, Bacterial / genetics, immunology*, metabolism*, pathology Mice Mice, Inbred C57BL Mice, Knockout Neisseria / physiology Receptors, TNF-Related Apoptosis-Inducing Ligand / metabolism Recombinant Proteins / pharmacology Solubility Survival Rate TNF-Related Apoptosis-Inducing Ligand / cerebrospinal fluid, immunology*, metabolism, pharmacology |
| Chemical | |
Reg. No./Substance:
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0/Antigens, CD18; 0/Cytokines; 0/Receptors, TNF-Related Apoptosis-Inducing Ligand; 0/Recombinant Proteins; 0/TNF-Related Apoptosis-Inducing Ligand |
| Comments/Corrections | |
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