| First Author | Aziz MM | Year | 2009 |
| Journal | J Immunol | Volume | 182 |
| Issue | 11 | Pages | 7222-32 |
| PubMed ID | 19454719 | Mgi Jnum | J:148851 |
| Mgi Id | MGI:3847018 | Doi | 10.4049/jimmunol.0803711 |
| Citation | Aziz MM, et al. (2009) MFG-E8 attenuates intestinal inflammation in murine experimental colitis by modulating osteopontin-dependent alphavbeta3 integrin signaling. J Immunol 182(11):7222-32 |
| abstractText | MFG-E8 (milk fat globule-epidermal growth factor 8) deficiency is strongly associated with acquisition of immune-mediated disorders due to the loss of tissue homeostasis. However, comparatively little is known regarding its functions in gastrointestinal tract disorders, in which immune homeostasis is a major concern. Herein, we report altered MFG-E8 expression in inflamed colons during the acute phase of murine experimental colitis and found that treatment with recombinant MFG-E8, but not its arginine-glycine-aspartate mutant counterpart, ameliorated colitis by reducing inflammation and improving disease parameters. To reveal the MFG-E8-mediated antiinflammatory mechanism, we employed an in vitro system, which showed the down-regulation of NF-kappaB in an LPS-dependent manner. Additionally, MFG-E8 altered alpha(v)beta(3) integrin-mediated focal adhesion kinase phosphorylation by impeding the binding of one of its potent ligands osteopontin, which becomes activated during colitis. Taken together, our results indicated that MFG-E8 has a novel therapeutic potential for treatment of colitis. |
