MFG-E8 attenuates intestinal inflammation in murine experimental colitis by modulating osteopontin-dependent alphavbeta3 integrin signaling
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 i...
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| Veröffentlicht in: | The Journal of immunology (1950) 2009-06, Vol.182 (11), p.7222-7232 |
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| container_title | The Journal of immunology (1950) |
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| creator | Aziz, Md Monowar Ishihara, Shunji Mishima, Yoshiyuki Oshima, Naoki Moriyama, Ichiro Yuki, Takafumi Kadowaki, Yasunori Rumi, Mohammad Azharul Karim Amano, Yuji Kinoshita, Yoshikazu |
| description | 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. |
| doi_str_mv | 10.4049/jimmunol.0803711 |
| format | Article |
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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.</description><identifier>EISSN: 1550-6606</identifier><identifier>DOI: 10.4049/jimmunol.0803711</identifier><identifier>PMID: 19454719</identifier><language>eng</language><publisher>United States</publisher><subject>Animals ; Antigens, Surface - analysis ; Antigens, Surface - pharmacology ; Colitis ; Disease Models, Animal ; Focal Adhesion Protein-Tyrosine Kinases - metabolism ; Inflammation ; Integrin alphaVbeta3 - metabolism ; Intestines - pathology ; Mice ; Milk Proteins - analysis ; Milk Proteins - pharmacology ; NF-kappa B - analysis ; Osteopontin - metabolism ; Phosphorylation ; Signal Transduction - drug effects</subject><ispartof>The Journal of immunology (1950), 2009-06, Vol.182 (11), p.7222-7232</ispartof><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/19454719$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Aziz, Md Monowar</creatorcontrib><creatorcontrib>Ishihara, Shunji</creatorcontrib><creatorcontrib>Mishima, Yoshiyuki</creatorcontrib><creatorcontrib>Oshima, Naoki</creatorcontrib><creatorcontrib>Moriyama, Ichiro</creatorcontrib><creatorcontrib>Yuki, Takafumi</creatorcontrib><creatorcontrib>Kadowaki, Yasunori</creatorcontrib><creatorcontrib>Rumi, Mohammad Azharul Karim</creatorcontrib><creatorcontrib>Amano, Yuji</creatorcontrib><creatorcontrib>Kinoshita, Yoshikazu</creatorcontrib><title>MFG-E8 attenuates intestinal inflammation in murine experimental colitis by modulating osteopontin-dependent alphavbeta3 integrin signaling</title><title>The Journal of immunology (1950)</title><addtitle>J Immunol</addtitle><description>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.</description><subject>Animals</subject><subject>Antigens, Surface - analysis</subject><subject>Antigens, Surface - pharmacology</subject><subject>Colitis</subject><subject>Disease Models, Animal</subject><subject>Focal Adhesion Protein-Tyrosine Kinases - metabolism</subject><subject>Inflammation</subject><subject>Integrin alphaVbeta3 - metabolism</subject><subject>Intestines - pathology</subject><subject>Mice</subject><subject>Milk Proteins - analysis</subject><subject>Milk Proteins - pharmacology</subject><subject>NF-kappa B - analysis</subject><subject>Osteopontin - metabolism</subject><subject>Phosphorylation</subject><subject>Signal Transduction - drug effects</subject><issn>1550-6606</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2009</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNo1kD9PwzAQxS0kREthZ0Ke2FJsx46TEVVtQSpi6R7ZsVNc-U-IHUQ_A18aC8pyd0_63Z3eA-AOoyVFtHk8GucmH-wS1ajkGF-AOWYMFVWFqhm4jvGIEKoQoVdghhvKKMfNHHy_brbFuoYiJe0nkXSExueajBc2j70Vzolkgs8Cumk0XkP9NejROO1TZrpgTTIRyhN0QU02w_4AQ0w6DMFnUSg9aK8yDYUd3sWn1EmUv28O-RyM5pB_5aUbcNkLG_XtuS_AfrPer56L3dv2ZfW0KwZGm4JzKTvBWVezDlGpmMR9rwmRQvaCSkEUp7xSmNVMYNQz3DGKCFcdI7gkEpcL8PB3dhjDx5Stts7ETlsrvA5TbCtOOM3pZPD-DE7SadUO2bMYT-1_euUPqLJ1jg</recordid><startdate>20090601</startdate><enddate>20090601</enddate><creator>Aziz, Md Monowar</creator><creator>Ishihara, Shunji</creator><creator>Mishima, Yoshiyuki</creator><creator>Oshima, Naoki</creator><creator>Moriyama, Ichiro</creator><creator>Yuki, Takafumi</creator><creator>Kadowaki, Yasunori</creator><creator>Rumi, Mohammad Azharul Karim</creator><creator>Amano, Yuji</creator><creator>Kinoshita, Yoshikazu</creator><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>7X8</scope></search><sort><creationdate>20090601</creationdate><title>MFG-E8 attenuates intestinal inflammation in murine experimental colitis by modulating osteopontin-dependent alphavbeta3 integrin signaling</title><author>Aziz, Md Monowar ; Ishihara, Shunji ; Mishima, Yoshiyuki ; Oshima, Naoki ; Moriyama, Ichiro ; Yuki, Takafumi ; Kadowaki, Yasunori ; Rumi, Mohammad Azharul Karim ; Amano, Yuji ; Kinoshita, Yoshikazu</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-p549-77bbca75c85c04bd5b1ffe22babfa4ba2d7476d1585a10f51c54027dc52132b13</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2009</creationdate><topic>Animals</topic><topic>Antigens, Surface - analysis</topic><topic>Antigens, Surface - pharmacology</topic><topic>Colitis</topic><topic>Disease Models, Animal</topic><topic>Focal Adhesion Protein-Tyrosine Kinases - metabolism</topic><topic>Inflammation</topic><topic>Integrin alphaVbeta3 - metabolism</topic><topic>Intestines - pathology</topic><topic>Mice</topic><topic>Milk Proteins - analysis</topic><topic>Milk Proteins - pharmacology</topic><topic>NF-kappa B - analysis</topic><topic>Osteopontin - metabolism</topic><topic>Phosphorylation</topic><topic>Signal Transduction - drug effects</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Aziz, Md Monowar</creatorcontrib><creatorcontrib>Ishihara, Shunji</creatorcontrib><creatorcontrib>Mishima, Yoshiyuki</creatorcontrib><creatorcontrib>Oshima, Naoki</creatorcontrib><creatorcontrib>Moriyama, Ichiro</creatorcontrib><creatorcontrib>Yuki, Takafumi</creatorcontrib><creatorcontrib>Kadowaki, Yasunori</creatorcontrib><creatorcontrib>Rumi, Mohammad Azharul Karim</creatorcontrib><creatorcontrib>Amano, Yuji</creatorcontrib><creatorcontrib>Kinoshita, Yoshikazu</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>MEDLINE - Academic</collection><jtitle>The Journal of immunology (1950)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Aziz, Md Monowar</au><au>Ishihara, Shunji</au><au>Mishima, Yoshiyuki</au><au>Oshima, Naoki</au><au>Moriyama, Ichiro</au><au>Yuki, Takafumi</au><au>Kadowaki, Yasunori</au><au>Rumi, Mohammad Azharul Karim</au><au>Amano, Yuji</au><au>Kinoshita, Yoshikazu</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>MFG-E8 attenuates intestinal inflammation in murine experimental colitis by modulating osteopontin-dependent alphavbeta3 integrin signaling</atitle><jtitle>The Journal of immunology (1950)</jtitle><addtitle>J Immunol</addtitle><date>2009-06-01</date><risdate>2009</risdate><volume>182</volume><issue>11</issue><spage>7222</spage><epage>7232</epage><pages>7222-7232</pages><eissn>1550-6606</eissn><abstract>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.</abstract><cop>United States</cop><pmid>19454719</pmid><doi>10.4049/jimmunol.0803711</doi><tpages>11</tpages></addata></record> |
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| source | MEDLINE; EZB-FREE-00999 freely available EZB journals; Alma/SFX Local Collection |
| subjects | Animals Antigens, Surface - analysis Antigens, Surface - pharmacology Colitis Disease Models, Animal Focal Adhesion Protein-Tyrosine Kinases - metabolism Inflammation Integrin alphaVbeta3 - metabolism Intestines - pathology Mice Milk Proteins - analysis Milk Proteins - pharmacology NF-kappa B - analysis Osteopontin - metabolism Phosphorylation Signal Transduction - drug effects |
| title | MFG-E8 attenuates intestinal inflammation in murine experimental colitis by modulating osteopontin-dependent alphavbeta3 integrin signaling |
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