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

Md. M. Aziz | Zendy; Shunji Ishihara | Zendy; Yoshiyuki Mishima | Zendy; Naoki Oshima | Zendy; Ichiro Moriyama | Zendy; Takafumi Yuki | Zendy; Yasunori Kadowaki | Zendy; M. A. Karim Rumi | Zendy; Yuji Amano | Zendy; Yoshikazu Kinoshita | Zendy

Open Access

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

Author(s) -

Md. M. Aziz,

Shunji Ishihara,

Yoshiyuki Mishima,

Naoki Oshima,

Ichiro Moriyama,

Takafumi Yuki,

Yasunori Kadowaki,

M. A. Karim Rumi,

Yuji Amano,

Yoshikazu Kinoshita

Publication year - 2009

Publication title -

the journal of immunology

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 2.737

H-Index - 372

eISSN - 1550-6606

pISSN - 0022-1767

DOI - 10.4049/jimmunol.0803711

Subject(s) - colitis , osteopontin , inflammation , immune system , integrin , inflammatory bowel disease , phosphorylation , homeostasis , immunology , gastrointestinal tract , chemistry , biology , cancer research , microbiology and biotechnology , medicine , receptor , biochemistry , disease

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.

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