Investigation regarding the role of MFG-E8 on NF-κB-dependent intestinal inflammation : Development of a new anti-inflammatory targeting MFG-E8
| Project/Area Number |
20590723
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Gastroenterology
|
|---|
| Research Institution | Shimane University |
|---|
Principal Investigator |
ISHIHARA Shunji Shimane University, 医学部, 准教授 (80263531)
|
|---|
| Project Period (FY) |
2008 – 2010
|
| Project Status |
Completed (Fiscal Year 2010)
|
| Budget Amount *help |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2010: ¥520,000 (Direct Cost: ¥400,000、Indirect Cost: ¥120,000)
Fiscal Year 2009: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2008: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
|
|---|
| Keywords | 炎症性腸疾患 / 自然免疫 / MFG-E8 / Toll受容体 / NF-κB / Tool受容体 / MF-κB / MF-кB |
|---|
| Research Abstract |
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.
|
Report
(4 results)
Research Products
(48 results)
-
-
-
[Journal Article] Decreased production of interleukin-10 and transforming growth factor-β in Toll-like receptor-activated intestinal B cells in SAMP1/Yit mice.2010
Author(s)
Mishima Y, Ishihara S, Aziz MM, Oka A, Kusunoki R, Otani A, Tada Y, Li YY, Moriyama I, Oshima N, Yuki T, Amano Y, Matsumoto S, Kinoshita Y
-
Journal Title
Immunology. 131
Pages: 473-487
Related Report
-
-
-
-
-
-
-
-
-
-
-
-
-
-
[Journal Article] Prolactin induces MFG-E8 production in macrophages via transcription factor C/EBPβ-dependent pathway.2008
Author(s)
Aziz MM, Ishihara S, Rumi MA, Mishima Yo, Oshima N, Kadota C, Moriyama I, Li YY, Rahman FB, Otani A, Oka A, Ishimura N, Kadowaki Y, Amano Y, Kinoshita Y
-
Journal Title
Apoptosis 13
Pages: 609-620
Related Report
-
-
-
-
-
-
-
-
-
-
-
-
[Presentation] Intestinal inflammation down-regulates SIGIRR/TIR8 expression in epithelial cells by inhibiting SP1-mediated pathway.2010
Author(s)
Kadota C, Ishihara S, Mishima Y, Oshima N, Oka A, Kusunoki R, Tada Y, Moriyama I, Yuki T, Kinoshita Y
Organizer
Digestive Disease Week.
Place of Presentation
New Orleans, USA
Related Report
-
[Presentation] Crosstalk between TLR5 and Notch1 signaling in epithelial cells during intestinal inflammation.2010
Author(s)
Yuki T, Ishihara S, Aziz MM, Mishima Y, Oshima N, Otani A, Oka A, Kusunoki R, Tada Y, Moriyama I, Yoshikazu K
Place of Presentation
New Orleans, USA
Related Report
-
-
-
-
-
-
-
-
[Presentation] Decreased production of IL-10 and TGF-β in TLR-activated intestinal B cells in SAMP1/Yit mice.2009
Author(s)
Mishima Y, Ishihara S, Aziz M, Oshima N, Otani A, Oka A, Kusunoki R, Moriyama I, Amano Y, Kinoshita Y
Organizer
Digestive Disease Week 2009
Place of Presentation
Chicago, USA
Related Report
-
-
[Presentation] Crosstalk between Notch and toll signaling in murine colitis.2009
Author(s)
Ishihara S, Aziz M, Mishima Y, Oshima N, Otani A, Oka A, Kusunoki R, Moriyama I, Ishimura M, Li YY, Amano Y, Kinoshita Y
Organizer
Digestive Disease Week 2009
Place of Presentation
Chicago, USA
Related Report
-
-
-
-
-
-
[Presentation] Milk fat globule EGF-8 attenuates intestinal inflammation in murine experimental colitis via inhibition of NF-κB activation.2008
Author(s)
Ishihara S, Aziz M, Rumi MA, Oshima N, Mishima Y, Kadota C, Otani A, Oka A, Norihisa I, Moriyama I, Kadowaki Y, Amano Y, Kinoshita Y
Organizer
Digestive Disease Week 2008
Place of Presentation
San Diego, USA
Related Report
-
[Presentation] A20 is an early responsive negative regulator of Toll-like receptor signaling in intestinal epithelial cells during inflammation.2008
Author(s)
Oshima N, Ishihara S, Rumi MAK, Aziz MM, Mishima Yo, Kadota C, Moriyama I, Ohtani A, Oka A, Li YY, Kadowaki Y, AmanoY, Kinoshita Y
Organizer
Digestive Disease Week 2008
Place of Presentation
San Diego, USA
Related Report
-
[Presentation] Intestinal CD5^+ B cells produce IL-10 and TGF-β via Toll-like receptor-mediated signaling.2008
Author(s)
Mishima Y, Ishihara S, Aziz MM, Rumi MAK, Oshima N, Kadota C, Moriyama I, Li YY, Ohtani A, Oka A, Kadowaki Y, Amano Y, Kinoshita Y
Organizer
Digestive Disease Week 2008
Place of Presentation
San Diego, USA
Related Report
