ReferenceID 19
Inhibition of bone morphogenetic protein signaling attenuates anemia associated with inflammation
Blood
Anemia of inflammation develops in settings of chronic inflammatory, infectious, or neoplastic disease. In this highly prevalent form of anemia, inflammatory cytokines, including IL-6, stimulate hepatic expression of he
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Record Fields
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- Reference Id
- 19
- Evidence Id
- 16609
- Core Evidence Id
- 16609
- Source Reference Id
- 36
- Herb2 Reference Id
- HBREF000096
- Subject Paper Key
- HERB005260_21393479
- Pubmed Id
- 21393479
- Doi
- 10.1182/blood-2010-10-313064
- Paper Title
- Inhibition of bone morphogenetic protein signaling attenuates anemia associated with inflammation
- Paper Abstract
- Anemia of inflammation develops in settings of chronic inflammatory, infectious, or neoplastic disease. In this highly prevalent form of anemia, inflammatory cytokines, including IL-6, stimulate hepatic expression of hepcidin, which negatively regulates iron bioavailability by inactivating ferroportin. Hepcidin is transcriptionally regulated by IL-6 and bone morphogenetic protein (BMP) signaling. We hypothesized that inhibiting BMP signaling can reduce hepcidin expression and ameliorate hypoferremia and anemia associated with inflammation. In human hepatoma cells, IL-6-induced hepcidin expression, an effect that was inhibited by treatment with a BMP type I receptor inhibitor, LDN-193189, or BMP ligand antagonists noggin and ALK3-Fc. In zebrafish, the induction of hepcidin expression by transgenic expression of IL-6 was also reduced by LDN-193189. In mice, treatment with IL-6 or turpentine increased hepcidin expression and reduced serum iron, effects that were inhibited by LDN-193189 or ALK3-Fc. Chronic turpentine treatment led to microcytic anemia, which was prevented by concurrent administration of LDN-193189 or attenuated when LDN-193189 was administered after anemia was established. Our studies support the concept that BMP and IL-6 act together to regulate iron homeostasis and suggest that inhibition of BMP signaling may be an effective strategy for the treatment of anemia of inflammation.
- Journal
- Blood
- Publish Year
- 2011
- Experiment Subject
- mouse
- Experiment Type
- Animal Experiment
- Phenotype Related
- Paper Title Cn
- Paper Title En
- Inhibition of bone morphogenetic protein signaling attenuates anemia associated with inflammation
- Bilingual Status
- semi_complete