Abstract
Macrophages undergo apoptosis as a mechanism of regulating their activation and the inflammatory reaction. Macrophages express the Corticotropin-Releasing Factor Receptor-2 (CRFR2) the endogenous agonists of which, the urocortins, are also present at the site of inflammation. We have found that urocortins induced macrophage apoptosis in a dose- and time-dependent manner via CRFR2. In contrast to lipopolysaccharide (LPS)-induced apoptosis, the pro-apoptosis pathway activated by urocortins involved the pro-apoptotic Bax and Bad proteins and not nitric oxide, JNK and p38MAPK characteristic of LPS. In conclusion, our data suggest that endogenous CRFR2 ligands exert an anti-inflammatory effect via induction of macrophage apoptosis.
MeSH terms
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Animals
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Apoptosis*
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Carrier Proteins / metabolism
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Cells, Cultured
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Corticotropin-Releasing Hormone / pharmacology*
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Inflammation / metabolism
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JNK Mitogen-Activated Protein Kinases / metabolism
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Lipopolysaccharides / pharmacology
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Macrophages / drug effects*
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Macrophages / metabolism
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Mice
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Polysaccharides, Bacterial / pharmacology
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Proto-Oncogene Proteins c-bcl-2 / metabolism
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Receptors, Corticotropin-Releasing Hormone / antagonists & inhibitors
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Receptors, Corticotropin-Releasing Hormone / metabolism*
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Signal Transduction
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Urocortins
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bcl-2-Associated X Protein
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bcl-Associated Death Protein
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p38 Mitogen-Activated Protein Kinases / metabolism
Substances
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Bad protein, mouse
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Bax protein, mouse
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CRF receptor type 2
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Carrier Proteins
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Lipopolysaccharides
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Polysaccharides, Bacterial
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Proto-Oncogene Proteins c-bcl-2
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Receptors, Corticotropin-Releasing Hormone
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Urocortins
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bcl-2-Associated X Protein
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bcl-Associated Death Protein
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urocortin 2, mouse
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Corticotropin-Releasing Hormone
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JNK Mitogen-Activated Protein Kinases
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p38 Mitogen-Activated Protein Kinases