| Added by | liaudet-coopman |
|---|---|
| Group name | EquipeELC |
| Item Type | Journal Article |
| Title | Cherubism allele heterozygosity amplifies microbe-induced inflammatory responses in murine macrophages |
| Creator | Prod'Homme et al. |
| Author | Virginie Prod'Homme |
| Author | Laurent Boyer |
| Author | Nicholas Dubois |
| Author | Aude Mallavialle |
| Author | Patrick Munro |
| Author | Xavier Mouska |
| Author | Isabelle Coste |
| Author | Robert Rottapel |
| Author | Sophie Tartare-Deckert |
| Author | Marcel Deckert |
| Abstract | Cherubism is a rare autoinflammatory bone disorder that is associated with point mutations in the SH3-domain binding protein 2 (SH3BP2) gene, which encodes the adapter protein 3BP2. Individuals with cherubism present with symmetrical fibro-osseous lesions of the jaw, which are attributed to exacerbated osteoclast activation and defective osteoblast differentiation. Although it is a dominant trait in humans, cherubism appears to be recessively transmitted in mice, suggesting the existence of additional factors in the pathogenesis of cherubism. Here, we report that macrophages from 3BP2-deficient mice exhibited dramatically reduced inflammatory responses to microbial challenge and reduced phagocytosis. 3BP2 was necessary for LPS-induced activation of signaling pathways involved in macrophage function, including SRC, VAV1, p38MAPK, IKK?/?, RAC, and actin polymerization pathways. Conversely, we demonstrated that the presence of a single Sh3bp2 cherubic allele and pathogen-associated molecular pattern (PAMP) stimulation had a strong cooperative effect on macrophage activation and inflammatory responses in mice. Together, the results from our study in murine genetic models support the notion that infection may represent a driver event in the etiology of cherubism in humans and suggest limiting inflammation in affected individuals may reduce manifestation of cherubic lesions. |
| Publication | The Journal of Clinical Investigation |
| Volume | 125 |
| Issue | 4 |
| Pages | 1396-1400 |
| Date | Apr 2015 |
| Journal Abbr | J. Clin. Invest. |
| Language | eng |
| DOI | 10.1172/JCI71081 |
| ISSN | 1558-8238 |
| Library Catalog | PubMed |
| Extra | PMID: 25705883 PMCID: PMC4396483 |
| Tags | Actins, Adaptor Proteins, Signal Transducing, Adoptive Transfer, Amino Acid Substitution, Animals, Cherubism, Cytokines, Disease Models, Animal, Heterozygote, Humans, Inflammation, Lipopolysaccharides, Macrophage Activation, Macrophages, Peritoneal, Mice, Mice, Inbred C57BL, Mice, Knockout, Mutagenesis, Site-Directed, Mutation, Missense, original, Osteoclasts, Phagocytosis, Point Mutation, Toll-Like Receptor 4 |
| Date Added | 2018/09/26 - 14:32:52 |
| Date Modified | 2019/05/29 - 12:13:28 |
Institut de Recherche en Cancérologie de
