Investigation regarding the role of MFG-E8 on NF-κB-dependent intestinal inflammation : Development of a new anti-inflammatory targeting MFG-E8

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MFG-E8 deficiency is associated with acquisition of immune-mediated disorders due to the loss of tissue homeostasis. We observed 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 RGD 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 downregulation of NF-κB in an LPS dependent manner. In addition, MFG-E8 altered α_vβ_3-integrin-mediated FAK phosphorylation by impeding the binding of one of its potent ligands osteopontin, which becomes activated during colitis. Our results indicated that MFG-E8 has a novel therapeutic potential for treatment of colitis.Recently, we also employed mfg-e8 KO mice for evaluating the function of MFG-E8 on intestinal inflammation. Acute experimental colitis was established by administrating of dextran sodium sulphate (DSS). We found that exacerbation of body weight loss, shorting of colon and histological inflammation in mfg-e8 KO mice during DSS-induced intestinal inflammation, as compared to those in wild mice. Additional investigations will be necessary to elucidate the role of MFG-E8 in chronic intestinal inflammation.