MFG-E8 Attenuates Intestinal Inflammation in Murine Experimental Colitis by Modulating Osteopontin-Dependent αvβ3 Integrin Signaling

作者: Md. Monowar Aziz , Shunji Ishihara , Yoshiyuki Mishima , Naoki Oshima , Ichiro Moriyama

DOI: 10.4049/JIMMUNOL.0803711

关键词: Growth factorFocal adhesionOsteopontinCancer researchPhosphorylationColitisBiologyInflammationAlpha (ethology)ImmunologyTissue homeostasis

摘要: MFG-E8 (milk fat globule-epidermal growth factor 8) deficiency is strongly associated with acquisition of immune-mediated disorders due to the loss tissue homeostasis. However, comparatively little known regarding its functions in gastrointestinal tract disorders, which immune homeostasis a major concern. Herein, we report altered expression inflamed colons during acute phase murine experimental colitis and found that treatment recombinant MFG-E8, but not arginine-glycine-aspartate mutant counterpart, ameliorated by reducing inflammation improving disease parameters. To reveal MFG-E8-mediated antiinflammatory mechanism, employed an vitro system, showed down-regulation NF-kappaB LPS-dependent manner. Additionally, alpha(v)beta(3) integrin-mediated focal adhesion kinase phosphorylation impeding binding one potent ligands osteopontin, becomes activated colitis. Taken together, our results indicated has novel therapeutic potential for

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