Journal
JOURNAL OF IMMUNOLOGY
Volume 182, Issue 11, Pages 7222-7232Publisher
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.0803711
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- Ministry of Education, Science, Sports, and Culture of Japan
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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 anti-inflammatory mechanism, we employed an in vitro system, which showed the down-regulation of NF-kappa B 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. The Journal of Immunology, 2009, 182: 7222-7232.
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