Oligosaccharides from agar inhibit murine intestinal inflammation through the induction of heme oxygenase-1 expression
Background Agarose is hydrolyzed easily to yield oligosaccharides, designated as agaro-oligosaccharides (AGOs). Recently, it has been demonstrated that AGOs induce heme oxygenase-1 (HO-1) expression in macrophages and that they might lead to anti-inflammatory property. Nevertheless, the molecular me...
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| Veröffentlicht in: | Journal of gastroenterology 2013-08, Vol.48 (8), p.897-909 |
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| creator | Higashimura, Yasuki Naito, Yuji Takagi, Tomohisa Mizushima, Katsura Hirai, Yasuko Harusato, Akihito Ohnogi, Hiromu Yamaji, Ryoichi Inui, Hiroshi Nakano, Yoshihisa Yoshikawa, Toshikazu |
| description | Background
Agarose is hydrolyzed easily to yield oligosaccharides, designated as agaro-oligosaccharides (AGOs). Recently, it has been demonstrated that AGOs induce heme oxygenase-1 (HO-1) expression in macrophages and that they might lead to anti-inflammatory property. Nevertheless, the molecular mechanism of AGO-mediated HO-1 induction remains unknown, as does AGOs’ ability to elicit anti-inflammatory activity in vivo. This study was undertaken to uncover the mechanism of AGO-mediated HO-1 induction and to investigate the therapeutic effect of AGOs on intestinal inflammation.
Methods
Mice were treated with 2,4,6-trinitrobenzene sulfonic acid (TNBS) to induce colitis. The respective degrees of mucosal injury of mice that had received AGO and control mice were compared. We investigated HO-1 expression using Western blotting, quantitative real-time PCR (qRT-PCR), and immunohistochemistry. The expression of tumor necrosis factor-α (TNF-α) was measured using qRT-PCR and enzyme-linked immunosorbent assay.
Results
AGO administration induced HO-1 expression in colonic mucosa. The induction was observed mainly in F4/80 positive macrophages. Increased colonic damage and myeloperoxidase activity after TNBS treatment were inhibited by AGO administration. TNBS treatment induced TNF-α expression, and AGO administration suppressed induction. However, HO inhibitor canceled AGO-mediated amelioration of colitis. In RAW264 cells, AGOs enhanced HO-1 expression time-dependently and concentration-dependently and suppressed lipopolysaccharide-induced TNF-α expression. Furthermore, agarotetraose-mediated HO-1 induction required NF-E2-related factor 2 function and phosphorylation of c-jun N-terminal kinase.
Conclusions
We infer that AGO administration inhibits TNBS-induced colitis in mice through HO-1 induction in macrophages. Consequently, oral administration of AGOs might be an important therapeutic strategy for inflammatory bowel disease. |
| doi_str_mv | 10.1007/s00535-012-0719-4 |
| format | Article |
| fullrecord | <record><control><sourceid>gale_proqu</sourceid><recordid>TN_cdi_proquest_journals_1423255997</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><galeid>A714585592</galeid><sourcerecordid>A714585592</sourcerecordid><originalsourceid>FETCH-LOGICAL-c558t-152e6f20e2c793fd7c49bdb86e4efcb4818f721022f185e40d716f1579189a973</originalsourceid><addsrcrecordid>eNp1kU1v1DAQhi0EokvhB3BBkTineBx7bR-rii-pUi9wthxnnLiK48VOUPvv62ULKhLIh_HMPO9oRi8hb4FeAKXyQ6FUdKKlwFoqQbf8GdkBrxWhGXtOdlRz3gJIfkZelXJLKXRUqJfkjHWgFNXdjvy8mcOYinVusjkMWBqfU2zsaHMTlin0YW3ilsOCNV2xrGGxc_362cZo15CWZp1y2sapxiMzbO5XNflmwohNursfcbEFW2jw7pCxlNp-TV54Oxd88xjPyfdPH79dfWmvbz5_vbq8bp0Qam1BMNx7RpE5qTs_SMd1P_Rqjxy967kC5SUDypgHJZDTQcLeg5AalLZadufk_WnuIacfW13f3KYt1xOKAc46JoR-So12RlOPS2u2LobizKUELlTFWKUu_kHVN2AMLi3oQ63_JYCTwOVUSkZvDjlEm-8NUHM00JwMNNVAczTQ8Kp597jw1kcc_ih-O1YBdgJKbS0j5icX_XfqA8Qfpd8</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1423255997</pqid></control><display><type>article</type><title>Oligosaccharides from agar inhibit murine intestinal inflammation through the induction of heme oxygenase-1 expression</title><source>MEDLINE</source><source>Springer Nature - Complete Springer Journals</source><creator>Higashimura, Yasuki ; Naito, Yuji ; Takagi, Tomohisa ; Mizushima, Katsura ; Hirai, Yasuko ; Harusato, Akihito ; Ohnogi, Hiromu ; Yamaji, Ryoichi ; Inui, Hiroshi ; Nakano, Yoshihisa ; Yoshikawa, Toshikazu</creator><creatorcontrib>Higashimura, Yasuki ; Naito, Yuji ; Takagi, Tomohisa ; Mizushima, Katsura ; Hirai, Yasuko ; Harusato, Akihito ; Ohnogi, Hiromu ; Yamaji, Ryoichi ; Inui, Hiroshi ; Nakano, Yoshihisa ; Yoshikawa, Toshikazu</creatorcontrib><description>Background
Agarose is hydrolyzed easily to yield oligosaccharides, designated as agaro-oligosaccharides (AGOs). Recently, it has been demonstrated that AGOs induce heme oxygenase-1 (HO-1) expression in macrophages and that they might lead to anti-inflammatory property. Nevertheless, the molecular mechanism of AGO-mediated HO-1 induction remains unknown, as does AGOs’ ability to elicit anti-inflammatory activity in vivo. This study was undertaken to uncover the mechanism of AGO-mediated HO-1 induction and to investigate the therapeutic effect of AGOs on intestinal inflammation.
Methods
Mice were treated with 2,4,6-trinitrobenzene sulfonic acid (TNBS) to induce colitis. The respective degrees of mucosal injury of mice that had received AGO and control mice were compared. We investigated HO-1 expression using Western blotting, quantitative real-time PCR (qRT-PCR), and immunohistochemistry. The expression of tumor necrosis factor-α (TNF-α) was measured using qRT-PCR and enzyme-linked immunosorbent assay.
Results
AGO administration induced HO-1 expression in colonic mucosa. The induction was observed mainly in F4/80 positive macrophages. Increased colonic damage and myeloperoxidase activity after TNBS treatment were inhibited by AGO administration. TNBS treatment induced TNF-α expression, and AGO administration suppressed induction. However, HO inhibitor canceled AGO-mediated amelioration of colitis. In RAW264 cells, AGOs enhanced HO-1 expression time-dependently and concentration-dependently and suppressed lipopolysaccharide-induced TNF-α expression. Furthermore, agarotetraose-mediated HO-1 induction required NF-E2-related factor 2 function and phosphorylation of c-jun N-terminal kinase.
Conclusions
We infer that AGO administration inhibits TNBS-induced colitis in mice through HO-1 induction in macrophages. Consequently, oral administration of AGOs might be an important therapeutic strategy for inflammatory bowel disease.</description><identifier>ISSN: 0944-1174</identifier><identifier>EISSN: 1435-5922</identifier><identifier>DOI: 10.1007/s00535-012-0719-4</identifier><identifier>PMID: 23188093</identifier><language>eng</language><publisher>Tokyo: Springer Japan</publisher><subject>Abdominal Surgery ; Animals ; Anti-Inflammatory Agents - administration & dosage ; Anti-Inflammatory Agents - chemistry ; Anti-Inflammatory Agents - pharmacology ; Blotting, Western ; Cell Line ; Colitis ; Colitis - physiopathology ; Colitis - prevention & control ; Colorectal Surgery ; Disease Models, Animal ; Dose-Response Relationship, Drug ; Enzyme-Linked Immunosorbent Assay ; Enzymes ; Gastroenterology ; Gastrointestinal diseases ; Health aspects ; Heme ; Heme Oxygenase-1 - genetics ; Heme Oxygenase-1 - metabolism ; Hepatology ; Inflammation ; Inflammation - physiopathology ; Inflammation - prevention & control ; Macrophages ; Macrophages - drug effects ; Macrophages - metabolism ; Male ; Medicine ; Medicine & Public Health ; Mice ; Mice, Inbred C57BL ; Oligosaccharides - administration & dosage ; Oligosaccharides - chemistry ; Oligosaccharides - pharmacology ; Original Article—Alimentary Tract ; Real-Time Polymerase Chain Reaction ; Sepharose - metabolism ; Surgical Oncology ; Time Factors ; Trinitrobenzenesulfonic Acid - toxicity</subject><ispartof>Journal of gastroenterology, 2013-08, Vol.48 (8), p.897-909</ispartof><rights>Springer Japan 2012</rights><rights>COPYRIGHT 2013 Springer</rights><rights>Springer Japan 2013</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c558t-152e6f20e2c793fd7c49bdb86e4efcb4818f721022f185e40d716f1579189a973</citedby><cites>FETCH-LOGICAL-c558t-152e6f20e2c793fd7c49bdb86e4efcb4818f721022f185e40d716f1579189a973</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s00535-012-0719-4$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s00535-012-0719-4$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,776,780,27901,27902,41464,42533,51294</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23188093$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Higashimura, Yasuki</creatorcontrib><creatorcontrib>Naito, Yuji</creatorcontrib><creatorcontrib>Takagi, Tomohisa</creatorcontrib><creatorcontrib>Mizushima, Katsura</creatorcontrib><creatorcontrib>Hirai, Yasuko</creatorcontrib><creatorcontrib>Harusato, Akihito</creatorcontrib><creatorcontrib>Ohnogi, Hiromu</creatorcontrib><creatorcontrib>Yamaji, Ryoichi</creatorcontrib><creatorcontrib>Inui, Hiroshi</creatorcontrib><creatorcontrib>Nakano, Yoshihisa</creatorcontrib><creatorcontrib>Yoshikawa, Toshikazu</creatorcontrib><title>Oligosaccharides from agar inhibit murine intestinal inflammation through the induction of heme oxygenase-1 expression</title><title>Journal of gastroenterology</title><addtitle>J Gastroenterol</addtitle><addtitle>J Gastroenterol</addtitle><description>Background
Agarose is hydrolyzed easily to yield oligosaccharides, designated as agaro-oligosaccharides (AGOs). Recently, it has been demonstrated that AGOs induce heme oxygenase-1 (HO-1) expression in macrophages and that they might lead to anti-inflammatory property. Nevertheless, the molecular mechanism of AGO-mediated HO-1 induction remains unknown, as does AGOs’ ability to elicit anti-inflammatory activity in vivo. This study was undertaken to uncover the mechanism of AGO-mediated HO-1 induction and to investigate the therapeutic effect of AGOs on intestinal inflammation.
Methods
Mice were treated with 2,4,6-trinitrobenzene sulfonic acid (TNBS) to induce colitis. The respective degrees of mucosal injury of mice that had received AGO and control mice were compared. We investigated HO-1 expression using Western blotting, quantitative real-time PCR (qRT-PCR), and immunohistochemistry. The expression of tumor necrosis factor-α (TNF-α) was measured using qRT-PCR and enzyme-linked immunosorbent assay.
Results
AGO administration induced HO-1 expression in colonic mucosa. The induction was observed mainly in F4/80 positive macrophages. Increased colonic damage and myeloperoxidase activity after TNBS treatment were inhibited by AGO administration. TNBS treatment induced TNF-α expression, and AGO administration suppressed induction. However, HO inhibitor canceled AGO-mediated amelioration of colitis. In RAW264 cells, AGOs enhanced HO-1 expression time-dependently and concentration-dependently and suppressed lipopolysaccharide-induced TNF-α expression. Furthermore, agarotetraose-mediated HO-1 induction required NF-E2-related factor 2 function and phosphorylation of c-jun N-terminal kinase.
Conclusions
We infer that AGO administration inhibits TNBS-induced colitis in mice through HO-1 induction in macrophages. Consequently, oral administration of AGOs might be an important therapeutic strategy for inflammatory bowel disease.</description><subject>Abdominal Surgery</subject><subject>Animals</subject><subject>Anti-Inflammatory Agents - administration & dosage</subject><subject>Anti-Inflammatory Agents - chemistry</subject><subject>Anti-Inflammatory Agents - pharmacology</subject><subject>Blotting, Western</subject><subject>Cell Line</subject><subject>Colitis</subject><subject>Colitis - physiopathology</subject><subject>Colitis - prevention & control</subject><subject>Colorectal Surgery</subject><subject>Disease Models, Animal</subject><subject>Dose-Response Relationship, Drug</subject><subject>Enzyme-Linked Immunosorbent Assay</subject><subject>Enzymes</subject><subject>Gastroenterology</subject><subject>Gastrointestinal diseases</subject><subject>Health aspects</subject><subject>Heme</subject><subject>Heme Oxygenase-1 - genetics</subject><subject>Heme Oxygenase-1 - metabolism</subject><subject>Hepatology</subject><subject>Inflammation</subject><subject>Inflammation - physiopathology</subject><subject>Inflammation - prevention & control</subject><subject>Macrophages</subject><subject>Macrophages - drug effects</subject><subject>Macrophages - metabolism</subject><subject>Male</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Oligosaccharides - administration & dosage</subject><subject>Oligosaccharides - chemistry</subject><subject>Oligosaccharides - pharmacology</subject><subject>Original Article—Alimentary Tract</subject><subject>Real-Time Polymerase Chain Reaction</subject><subject>Sepharose - metabolism</subject><subject>Surgical Oncology</subject><subject>Time Factors</subject><subject>Trinitrobenzenesulfonic Acid - toxicity</subject><issn>0944-1174</issn><issn>1435-5922</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNp1kU1v1DAQhi0EokvhB3BBkTineBx7bR-rii-pUi9wthxnnLiK48VOUPvv62ULKhLIh_HMPO9oRi8hb4FeAKXyQ6FUdKKlwFoqQbf8GdkBrxWhGXtOdlRz3gJIfkZelXJLKXRUqJfkjHWgFNXdjvy8mcOYinVusjkMWBqfU2zsaHMTlin0YW3ilsOCNV2xrGGxc_362cZo15CWZp1y2sapxiMzbO5XNflmwohNursfcbEFW2jw7pCxlNp-TV54Oxd88xjPyfdPH79dfWmvbz5_vbq8bp0Qam1BMNx7RpE5qTs_SMd1P_Rqjxy967kC5SUDypgHJZDTQcLeg5AalLZadufk_WnuIacfW13f3KYt1xOKAc46JoR-So12RlOPS2u2LobizKUELlTFWKUu_kHVN2AMLi3oQ63_JYCTwOVUSkZvDjlEm-8NUHM00JwMNNVAczTQ8Kp597jw1kcc_ih-O1YBdgJKbS0j5icX_XfqA8Qfpd8</recordid><startdate>20130801</startdate><enddate>20130801</enddate><creator>Higashimura, Yasuki</creator><creator>Naito, Yuji</creator><creator>Takagi, Tomohisa</creator><creator>Mizushima, Katsura</creator><creator>Hirai, Yasuko</creator><creator>Harusato, Akihito</creator><creator>Ohnogi, Hiromu</creator><creator>Yamaji, Ryoichi</creator><creator>Inui, Hiroshi</creator><creator>Nakano, Yoshihisa</creator><creator>Yoshikawa, Toshikazu</creator><general>Springer Japan</general><general>Springer</general><general>Springer Nature B.V</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7RV</scope><scope>7T5</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>H94</scope><scope>K9-</scope><scope>K9.</scope><scope>KB0</scope><scope>M0R</scope><scope>M0S</scope><scope>M1P</scope><scope>NAPCQ</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope></search><sort><creationdate>20130801</creationdate><title>Oligosaccharides from agar inhibit murine intestinal inflammation through the induction of heme oxygenase-1 expression</title><author>Higashimura, Yasuki ; Naito, Yuji ; Takagi, Tomohisa ; Mizushima, Katsura ; Hirai, Yasuko ; Harusato, Akihito ; Ohnogi, Hiromu ; Yamaji, Ryoichi ; Inui, Hiroshi ; Nakano, Yoshihisa ; Yoshikawa, Toshikazu</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c558t-152e6f20e2c793fd7c49bdb86e4efcb4818f721022f185e40d716f1579189a973</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Abdominal Surgery</topic><topic>Animals</topic><topic>Anti-Inflammatory Agents - administration & dosage</topic><topic>Anti-Inflammatory Agents - chemistry</topic><topic>Anti-Inflammatory Agents - pharmacology</topic><topic>Blotting, Western</topic><topic>Cell Line</topic><topic>Colitis</topic><topic>Colitis - physiopathology</topic><topic>Colitis - prevention & control</topic><topic>Colorectal Surgery</topic><topic>Disease Models, Animal</topic><topic>Dose-Response Relationship, Drug</topic><topic>Enzyme-Linked Immunosorbent Assay</topic><topic>Enzymes</topic><topic>Gastroenterology</topic><topic>Gastrointestinal diseases</topic><topic>Health aspects</topic><topic>Heme</topic><topic>Heme Oxygenase-1 - genetics</topic><topic>Heme Oxygenase-1 - metabolism</topic><topic>Hepatology</topic><topic>Inflammation</topic><topic>Inflammation - physiopathology</topic><topic>Inflammation - prevention & control</topic><topic>Macrophages</topic><topic>Macrophages - drug effects</topic><topic>Macrophages - metabolism</topic><topic>Male</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Oligosaccharides - administration & dosage</topic><topic>Oligosaccharides - chemistry</topic><topic>Oligosaccharides - pharmacology</topic><topic>Original Article—Alimentary Tract</topic><topic>Real-Time Polymerase Chain Reaction</topic><topic>Sepharose - metabolism</topic><topic>Surgical Oncology</topic><topic>Time Factors</topic><topic>Trinitrobenzenesulfonic Acid - toxicity</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Higashimura, Yasuki</creatorcontrib><creatorcontrib>Naito, Yuji</creatorcontrib><creatorcontrib>Takagi, Tomohisa</creatorcontrib><creatorcontrib>Mizushima, Katsura</creatorcontrib><creatorcontrib>Hirai, Yasuko</creatorcontrib><creatorcontrib>Harusato, Akihito</creatorcontrib><creatorcontrib>Ohnogi, Hiromu</creatorcontrib><creatorcontrib>Yamaji, Ryoichi</creatorcontrib><creatorcontrib>Inui, Hiroshi</creatorcontrib><creatorcontrib>Nakano, Yoshihisa</creatorcontrib><creatorcontrib>Yoshikawa, Toshikazu</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Nursing & Allied Health Database</collection><collection>Immunology Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Consumer Health Database (Alumni Edition)</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Consumer Health Database</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Nursing & Allied Health Premium</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><jtitle>Journal of gastroenterology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Higashimura, Yasuki</au><au>Naito, Yuji</au><au>Takagi, Tomohisa</au><au>Mizushima, Katsura</au><au>Hirai, Yasuko</au><au>Harusato, Akihito</au><au>Ohnogi, Hiromu</au><au>Yamaji, Ryoichi</au><au>Inui, Hiroshi</au><au>Nakano, Yoshihisa</au><au>Yoshikawa, Toshikazu</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Oligosaccharides from agar inhibit murine intestinal inflammation through the induction of heme oxygenase-1 expression</atitle><jtitle>Journal of gastroenterology</jtitle><stitle>J Gastroenterol</stitle><addtitle>J Gastroenterol</addtitle><date>2013-08-01</date><risdate>2013</risdate><volume>48</volume><issue>8</issue><spage>897</spage><epage>909</epage><pages>897-909</pages><issn>0944-1174</issn><eissn>1435-5922</eissn><abstract>Background
Agarose is hydrolyzed easily to yield oligosaccharides, designated as agaro-oligosaccharides (AGOs). Recently, it has been demonstrated that AGOs induce heme oxygenase-1 (HO-1) expression in macrophages and that they might lead to anti-inflammatory property. Nevertheless, the molecular mechanism of AGO-mediated HO-1 induction remains unknown, as does AGOs’ ability to elicit anti-inflammatory activity in vivo. This study was undertaken to uncover the mechanism of AGO-mediated HO-1 induction and to investigate the therapeutic effect of AGOs on intestinal inflammation.
Methods
Mice were treated with 2,4,6-trinitrobenzene sulfonic acid (TNBS) to induce colitis. The respective degrees of mucosal injury of mice that had received AGO and control mice were compared. We investigated HO-1 expression using Western blotting, quantitative real-time PCR (qRT-PCR), and immunohistochemistry. The expression of tumor necrosis factor-α (TNF-α) was measured using qRT-PCR and enzyme-linked immunosorbent assay.
Results
AGO administration induced HO-1 expression in colonic mucosa. The induction was observed mainly in F4/80 positive macrophages. Increased colonic damage and myeloperoxidase activity after TNBS treatment were inhibited by AGO administration. TNBS treatment induced TNF-α expression, and AGO administration suppressed induction. However, HO inhibitor canceled AGO-mediated amelioration of colitis. In RAW264 cells, AGOs enhanced HO-1 expression time-dependently and concentration-dependently and suppressed lipopolysaccharide-induced TNF-α expression. Furthermore, agarotetraose-mediated HO-1 induction required NF-E2-related factor 2 function and phosphorylation of c-jun N-terminal kinase.
Conclusions
We infer that AGO administration inhibits TNBS-induced colitis in mice through HO-1 induction in macrophages. Consequently, oral administration of AGOs might be an important therapeutic strategy for inflammatory bowel disease.</abstract><cop>Tokyo</cop><pub>Springer Japan</pub><pmid>23188093</pmid><doi>10.1007/s00535-012-0719-4</doi><tpages>13</tpages></addata></record> |
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| ispartof | Journal of gastroenterology, 2013-08, Vol.48 (8), p.897-909 |
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| source | MEDLINE; Springer Nature - Complete Springer Journals |
| subjects | Abdominal Surgery Animals Anti-Inflammatory Agents - administration & dosage Anti-Inflammatory Agents - chemistry Anti-Inflammatory Agents - pharmacology Blotting, Western Cell Line Colitis Colitis - physiopathology Colitis - prevention & control Colorectal Surgery Disease Models, Animal Dose-Response Relationship, Drug Enzyme-Linked Immunosorbent Assay Enzymes Gastroenterology Gastrointestinal diseases Health aspects Heme Heme Oxygenase-1 - genetics Heme Oxygenase-1 - metabolism Hepatology Inflammation Inflammation - physiopathology Inflammation - prevention & control Macrophages Macrophages - drug effects Macrophages - metabolism Male Medicine Medicine & Public Health Mice Mice, Inbred C57BL Oligosaccharides - administration & dosage Oligosaccharides - chemistry Oligosaccharides - pharmacology Original Article—Alimentary Tract Real-Time Polymerase Chain Reaction Sepharose - metabolism Surgical Oncology Time Factors Trinitrobenzenesulfonic Acid - toxicity |
| title | Oligosaccharides from agar inhibit murine intestinal inflammation through the induction of heme oxygenase-1 expression |
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