Dragon (repulsive guidance molecule B) inhibits IL-6 expression in macrophages

Xia, Y. and Cortez-Retamozo, V. and Niederkofler, V. and Salie, R. and Chen, S. and Samad, T. A. and Hong, C. C. and Arber, S. and Vyas, J. M. and Weissleder, R. and Pittet, M. J. and Lin, H. Y.. (2011) Dragon (repulsive guidance molecule B) inhibits IL-6 expression in macrophages. Journal of immunology, Vol. 186, H. 3. pp. 1369-1376.

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Official URL: http://edoc.unibas.ch/dok/A5844202

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Repulsive guidance molecule (RGM) family members RGMa, RGMb/Dragon, and RGMc/hemojuvelin were found recently to act as bone morphogenetic protein (BMP) coreceptors that enhance BMP signaling activity. Although our previous studies have shown that hemojuvelin regulates hepcidin expression and iron metabolism through the BMP pathway, the role of the BMP signaling mediated by Dragon remains largely unknown. We have shown previously that Dragon is expressed in neural cells, germ cells, and renal epithelial cells. In this study, we demonstrate that Dragon is highly expressed in macrophages. Studies with RAW264.7 and J774 macrophage cell lines reveal that Dragon negatively regulates IL-6 expression in a BMP ligand-dependent manner via the p38 MAPK and Erk1/2 pathways but not the Smad1/5/8 pathway. We also generated Dragon knockout mice and found that IL-6 is upregulated in macrophages and dendritic cells derived from whole lung tissue of these mice compared with that in respective cells derived from wild-type littermates. These results indicate that Dragon is an important negative regulator of IL-6 expression in immune cells and that Dragon-deficient mice may be a useful model for studying immune and inflammatory disorders.
Faculties and Departments:05 Faculty of Science > Departement Biozentrum > Neurobiology > Cell Biology (Arber)
UniBasel Contributors:Arber, Silvia
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:American Assoc. of Immunologists
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:08 Jun 2012 06:56
Deposited On:08 Jun 2012 06:52

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