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

被引：118

作者：

Aziz, Md. Monowar ^{[1
]}

Ishihara, Shunji ^{[1
]}

Mishima, Yoshiyuki ^{[1
]}

Oshima, Naoki ^{[1
]}

Moriyama, Ichiro ^{[1
]}

Yuki, Takafumi ^{[1
]}

Kadowaki, Yasunori ^{[1
]}

Rumi, Mohammad Azharul Karim ^{[2
]}

Amano, Yuji ^{[3
]}

Kinoshita, Yoshikazu ^{[1
]}

机构：

[1] Shimane Univ, Fac Med, Dept Internal Med 2, Sch Med, 89-1 Enya Cho, Izumo, Shimane, Japan

[2] Univ Kansas, Med Ctr, Dept Pathol & Lab Med, Kansas City, KS 66160 USA

[3] Shimane Univ Hosp, Div Gastrointestinal Endoscopy, Izumo, Shimane, Japan

来源：

JOURNAL OF IMMUNOLOGY | 2009年 / 182卷 / 11期

关键词：

FOCAL ADHESION KINASE; BOWEL-DISEASE; APOPTOTIC CELLS; CROHNS-DISEASE; IMMUNE-RESPONSE; KAPPA-B; MICE; ENGULFMENT; EXPRESSION; CYTOKINE;

D O I：

10.4049/jimmunol.0803711

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

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 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.

引用

页码：7222 / 7232

页数：11

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