Abstract
To investigate the role of C5a generated on complement activation in brain, the lupus model, MRL/lpr mice were treated with C5a receptor(R) antagonist (ant). Neutrophil infiltration, ICAM, TNF-alpha and iNOS mRNA expression, neuronal apoptosis and the expression of p-JNK, pSTAT1 and p-Erk were reduced and p-Akt increased on C5aR inhibition in MRL/lpr brains. MRL/lpr serum caused increased apoptosis in neurons showing that lupus had a direct effect on these cells. C5aRant pretreatment prevented the lupus serum induced loss of neuronal cells. Our findings demonstrate for the first time that C5a/C5aR signaling plays an important role in the pathogenesis of CNS lupus.
Copyright 2010. Published by Elsevier B.V.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Annexin A5 / metabolism
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Apoptosis / drug effects
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Brain / cytology
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Brain / metabolism*
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Cell Adhesion Molecules / genetics
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Cell Adhesion Molecules / metabolism
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Cells, Cultured
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Chemokine CXCL2 / genetics
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Chemokine CXCL2 / metabolism
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Complement C5a / therapeutic use*
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Disease Models, Animal
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Embryo, Mammalian
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In Situ Nick-End Labeling / methods
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Intercellular Adhesion Molecule-1 / metabolism
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Lupus Vasculitis, Central Nervous System / drug therapy*
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Lupus Vasculitis, Central Nervous System / pathology*
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Male
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Mice
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Mice, Inbred MRL lpr
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Neurons / drug effects
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Nitric Oxide Synthase Type II / genetics
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Nitric Oxide Synthase Type II / metabolism
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RNA, Messenger / metabolism
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Receptor, Anaphylatoxin C5a / genetics
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Receptor, Anaphylatoxin C5a / metabolism*
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Signal Transduction / drug effects
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Tumor Necrosis Factor-alpha / genetics
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Tumor Necrosis Factor-alpha / metabolism
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Up-Regulation / drug effects
Substances
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Annexin A5
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C5aRAD
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Cell Adhesion Molecules
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Chemokine CXCL2
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RNA, Messenger
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Receptor, Anaphylatoxin C5a
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Tumor Necrosis Factor-alpha
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Intercellular Adhesion Molecule-1
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Complement C5a
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Nitric Oxide Synthase Type II