Treatment with anti-interleukin-6 receptor antibody ameliorates intestinal polyposis in Apc(Min/+) mice under high-fat diet conditions
The prevalence of colorectal malignancies is increasing in the world. The parallel increase of metabolic syndrome gives a speculation between these two conditions, although the precise mechanism is still unclear. Interleukin-6 (IL-6) is a cytokine known to correlate with obesity and serve as a proin...
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creator | Yaoita, Takao Sasaki, Yu Yokozawa, Junji Sato, Takeshi Kanno, Nana Sakuta, Kazuhiro Yagi, Makoto Yoshizawa, Kazuya Iwano, Daisuke Nagino, Ko Nomura, Eiki Abe, Yasuhiko Nishise, Shoichi Takeda, Hiroaki Kawata, Sumio Ueno, Yoshiyuki |
description | The prevalence of colorectal malignancies is increasing in the world. The parallel increase of metabolic syndrome gives a speculation between these two conditions, although the precise mechanism is still unclear. Interleukin-6 (IL-6) is a cytokine known to correlate with obesity and serve as a proinflammatory adipokine. In the present study, we investigated the effect of IL-6 signaling blockade on intestinal polyp formation in obesity using a mouse model of adenomatous polyposis coli (Apc). Male C57BL/6J-Apc(Min/+) mice were fed a high-fat diet from 5 weeks of age, and the overweight mice thus obtained were given a weekly intraperitoneal injection of anti-mouse IL-6 receptor antibody (MR16-1) from 6 to 15 weeks of age, while control mice received IgG or phosphate-buffered saline (PBS). The total number of intestinal polyps was significantly decreased in the MR16-1-injected group (53.1 ± 6.8) relative to the control groups (PBS-injected, 81.3 ± 6.1; rat IgG-injected, 74.7 ± 4.8, p = 0.01), and in particular the number of polyps larger than 2 mm in diameter was markedly decreased. In addition, the mean diameter of polyps in the MR16-1-injected group was significantly smaller than that in the control groups. On the other hand, no significant differences in body weight, epididymal fat pad mass, or the plasma levels of glucose, insulin and triglyceride were observed among the three groups. Thus, treatment with anti-IL-6 receptor antibody suppressed polyp growth in obese Apc(Min/+) mice fed the high-fat diet. We suggest that IL-6 signaling may be responsible for the obesity-associated colorectal tumorigenesis. |
doi_str_mv | 10.1620/tjem.235.127 |
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The parallel increase of metabolic syndrome gives a speculation between these two conditions, although the precise mechanism is still unclear. Interleukin-6 (IL-6) is a cytokine known to correlate with obesity and serve as a proinflammatory adipokine. In the present study, we investigated the effect of IL-6 signaling blockade on intestinal polyp formation in obesity using a mouse model of adenomatous polyposis coli (Apc). Male C57BL/6J-Apc(Min/+) mice were fed a high-fat diet from 5 weeks of age, and the overweight mice thus obtained were given a weekly intraperitoneal injection of anti-mouse IL-6 receptor antibody (MR16-1) from 6 to 15 weeks of age, while control mice received IgG or phosphate-buffered saline (PBS). The total number of intestinal polyps was significantly decreased in the MR16-1-injected group (53.1 ± 6.8) relative to the control groups (PBS-injected, 81.3 ± 6.1; rat IgG-injected, 74.7 ± 4.8, p = 0.01), and in particular the number of polyps larger than 2 mm in diameter was markedly decreased. In addition, the mean diameter of polyps in the MR16-1-injected group was significantly smaller than that in the control groups. On the other hand, no significant differences in body weight, epididymal fat pad mass, or the plasma levels of glucose, insulin and triglyceride were observed among the three groups. Thus, treatment with anti-IL-6 receptor antibody suppressed polyp growth in obese Apc(Min/+) mice fed the high-fat diet. We suggest that IL-6 signaling may be responsible for the obesity-associated colorectal tumorigenesis.</description><identifier>EISSN: 1349-3329</identifier><identifier>DOI: 10.1620/tjem.235.127</identifier><identifier>PMID: 25746084</identifier><language>eng</language><publisher>Japan</publisher><subject>Adenomatous Polyposis Coli - genetics ; Animals ; Antibodies - administration & dosage ; Antibodies - pharmacology ; Antibodies - therapeutic use ; Blood Glucose - metabolism ; Diet, High-Fat ; Female ; Insulin - blood ; Intestinal Polyps - blood ; Intestinal Polyps - drug therapy ; Male ; Mice, Inbred C57BL ; Rats ; Receptors, Interleukin-6 - immunology ; Triglycerides - blood</subject><ispartof>Tohoku journal of experimental medicine, 2015-02, Vol.235 (2), p.127-134</ispartof><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>315,781,785,27926,27927</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25746084$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Yaoita, Takao</creatorcontrib><creatorcontrib>Sasaki, Yu</creatorcontrib><creatorcontrib>Yokozawa, Junji</creatorcontrib><creatorcontrib>Sato, Takeshi</creatorcontrib><creatorcontrib>Kanno, Nana</creatorcontrib><creatorcontrib>Sakuta, Kazuhiro</creatorcontrib><creatorcontrib>Yagi, Makoto</creatorcontrib><creatorcontrib>Yoshizawa, Kazuya</creatorcontrib><creatorcontrib>Iwano, Daisuke</creatorcontrib><creatorcontrib>Nagino, Ko</creatorcontrib><creatorcontrib>Nomura, Eiki</creatorcontrib><creatorcontrib>Abe, Yasuhiko</creatorcontrib><creatorcontrib>Nishise, Shoichi</creatorcontrib><creatorcontrib>Takeda, Hiroaki</creatorcontrib><creatorcontrib>Kawata, Sumio</creatorcontrib><creatorcontrib>Ueno, Yoshiyuki</creatorcontrib><title>Treatment with anti-interleukin-6 receptor antibody ameliorates intestinal polyposis in Apc(Min/+) mice under high-fat diet conditions</title><title>Tohoku journal of experimental medicine</title><addtitle>Tohoku J Exp Med</addtitle><description>The prevalence of colorectal malignancies is increasing in the world. The parallel increase of metabolic syndrome gives a speculation between these two conditions, although the precise mechanism is still unclear. Interleukin-6 (IL-6) is a cytokine known to correlate with obesity and serve as a proinflammatory adipokine. In the present study, we investigated the effect of IL-6 signaling blockade on intestinal polyp formation in obesity using a mouse model of adenomatous polyposis coli (Apc). Male C57BL/6J-Apc(Min/+) mice were fed a high-fat diet from 5 weeks of age, and the overweight mice thus obtained were given a weekly intraperitoneal injection of anti-mouse IL-6 receptor antibody (MR16-1) from 6 to 15 weeks of age, while control mice received IgG or phosphate-buffered saline (PBS). The total number of intestinal polyps was significantly decreased in the MR16-1-injected group (53.1 ± 6.8) relative to the control groups (PBS-injected, 81.3 ± 6.1; rat IgG-injected, 74.7 ± 4.8, p = 0.01), and in particular the number of polyps larger than 2 mm in diameter was markedly decreased. In addition, the mean diameter of polyps in the MR16-1-injected group was significantly smaller than that in the control groups. On the other hand, no significant differences in body weight, epididymal fat pad mass, or the plasma levels of glucose, insulin and triglyceride were observed among the three groups. Thus, treatment with anti-IL-6 receptor antibody suppressed polyp growth in obese Apc(Min/+) mice fed the high-fat diet. We suggest that IL-6 signaling may be responsible for the obesity-associated colorectal tumorigenesis.</description><subject>Adenomatous Polyposis Coli - genetics</subject><subject>Animals</subject><subject>Antibodies - administration & dosage</subject><subject>Antibodies - pharmacology</subject><subject>Antibodies - therapeutic use</subject><subject>Blood Glucose - metabolism</subject><subject>Diet, High-Fat</subject><subject>Female</subject><subject>Insulin - blood</subject><subject>Intestinal Polyps - blood</subject><subject>Intestinal Polyps - drug therapy</subject><subject>Male</subject><subject>Mice, Inbred C57BL</subject><subject>Rats</subject><subject>Receptors, Interleukin-6 - immunology</subject><subject>Triglycerides - blood</subject><issn>1349-3329</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNo1kE1LAzEQhoMgtlZvniXHimybj012cyziF1S81HPJbqY2dTdZkyzSP-Dvdqv1Mi_M-zAMD0JXlMyoZGSedtDOGBczyooTNKY8VxnnTI3QeYw7QnhOCnmGRkwUuSRlPkbfqwA6teAS_rJpi7VLNrMuQWig_7AukzhADV3y4bervNlj3UJjfdAJIj6wMVmnG9z5Zt_5aA9LvOjq6Yt189sb3NoacO8MBLy179tsoxM2FhKuvTM2We_iBTrd6CbC5TEn6O3hfnX3lC1fH5_vFsusY5SmjFfKKEZUrqGqNlRBsRFiGLlgvDJClEVNSlWUQipCQdWq1kIaw6Vig4VC8wma_t3tgv_sh8fXrY01NI124Pu4plJSVSpJ2YBeH9G-asGsu2BbHfbrf3f8B6WZcJ4</recordid><startdate>20150201</startdate><enddate>20150201</enddate><creator>Yaoita, Takao</creator><creator>Sasaki, Yu</creator><creator>Yokozawa, Junji</creator><creator>Sato, Takeshi</creator><creator>Kanno, Nana</creator><creator>Sakuta, Kazuhiro</creator><creator>Yagi, Makoto</creator><creator>Yoshizawa, Kazuya</creator><creator>Iwano, Daisuke</creator><creator>Nagino, Ko</creator><creator>Nomura, Eiki</creator><creator>Abe, Yasuhiko</creator><creator>Nishise, Shoichi</creator><creator>Takeda, Hiroaki</creator><creator>Kawata, Sumio</creator><creator>Ueno, Yoshiyuki</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>20150201</creationdate><title>Treatment with anti-interleukin-6 receptor antibody ameliorates intestinal polyposis in Apc(Min/+) mice under high-fat diet conditions</title><author>Yaoita, Takao ; Sasaki, Yu ; Yokozawa, Junji ; Sato, Takeshi ; Kanno, Nana ; Sakuta, Kazuhiro ; Yagi, Makoto ; Yoshizawa, Kazuya ; Iwano, Daisuke ; Nagino, Ko ; Nomura, Eiki ; Abe, Yasuhiko ; Nishise, Shoichi ; Takeda, Hiroaki ; Kawata, Sumio ; Ueno, Yoshiyuki</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-p211t-3b9d92094aebbf19e7f55e7f4523bd5587c0897856901e9c9ca56dd36923297a3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Adenomatous Polyposis Coli - genetics</topic><topic>Animals</topic><topic>Antibodies - administration & dosage</topic><topic>Antibodies - pharmacology</topic><topic>Antibodies - therapeutic use</topic><topic>Blood Glucose - metabolism</topic><topic>Diet, High-Fat</topic><topic>Female</topic><topic>Insulin - blood</topic><topic>Intestinal Polyps - blood</topic><topic>Intestinal Polyps - drug therapy</topic><topic>Male</topic><topic>Mice, Inbred C57BL</topic><topic>Rats</topic><topic>Receptors, Interleukin-6 - immunology</topic><topic>Triglycerides - blood</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Yaoita, Takao</creatorcontrib><creatorcontrib>Sasaki, Yu</creatorcontrib><creatorcontrib>Yokozawa, Junji</creatorcontrib><creatorcontrib>Sato, Takeshi</creatorcontrib><creatorcontrib>Kanno, Nana</creatorcontrib><creatorcontrib>Sakuta, Kazuhiro</creatorcontrib><creatorcontrib>Yagi, Makoto</creatorcontrib><creatorcontrib>Yoshizawa, Kazuya</creatorcontrib><creatorcontrib>Iwano, Daisuke</creatorcontrib><creatorcontrib>Nagino, Ko</creatorcontrib><creatorcontrib>Nomura, Eiki</creatorcontrib><creatorcontrib>Abe, Yasuhiko</creatorcontrib><creatorcontrib>Nishise, Shoichi</creatorcontrib><creatorcontrib>Takeda, Hiroaki</creatorcontrib><creatorcontrib>Kawata, Sumio</creatorcontrib><creatorcontrib>Ueno, Yoshiyuki</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>Tohoku journal of experimental medicine</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Yaoita, Takao</au><au>Sasaki, Yu</au><au>Yokozawa, Junji</au><au>Sato, Takeshi</au><au>Kanno, Nana</au><au>Sakuta, Kazuhiro</au><au>Yagi, Makoto</au><au>Yoshizawa, Kazuya</au><au>Iwano, Daisuke</au><au>Nagino, Ko</au><au>Nomura, Eiki</au><au>Abe, Yasuhiko</au><au>Nishise, Shoichi</au><au>Takeda, Hiroaki</au><au>Kawata, Sumio</au><au>Ueno, Yoshiyuki</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Treatment with anti-interleukin-6 receptor antibody ameliorates intestinal polyposis in Apc(Min/+) mice under high-fat diet conditions</atitle><jtitle>Tohoku journal of experimental medicine</jtitle><addtitle>Tohoku J Exp Med</addtitle><date>2015-02-01</date><risdate>2015</risdate><volume>235</volume><issue>2</issue><spage>127</spage><epage>134</epage><pages>127-134</pages><eissn>1349-3329</eissn><abstract>The prevalence of colorectal malignancies is increasing in the world. The parallel increase of metabolic syndrome gives a speculation between these two conditions, although the precise mechanism is still unclear. Interleukin-6 (IL-6) is a cytokine known to correlate with obesity and serve as a proinflammatory adipokine. In the present study, we investigated the effect of IL-6 signaling blockade on intestinal polyp formation in obesity using a mouse model of adenomatous polyposis coli (Apc). Male C57BL/6J-Apc(Min/+) mice were fed a high-fat diet from 5 weeks of age, and the overweight mice thus obtained were given a weekly intraperitoneal injection of anti-mouse IL-6 receptor antibody (MR16-1) from 6 to 15 weeks of age, while control mice received IgG or phosphate-buffered saline (PBS). The total number of intestinal polyps was significantly decreased in the MR16-1-injected group (53.1 ± 6.8) relative to the control groups (PBS-injected, 81.3 ± 6.1; rat IgG-injected, 74.7 ± 4.8, p = 0.01), and in particular the number of polyps larger than 2 mm in diameter was markedly decreased. In addition, the mean diameter of polyps in the MR16-1-injected group was significantly smaller than that in the control groups. On the other hand, no significant differences in body weight, epididymal fat pad mass, or the plasma levels of glucose, insulin and triglyceride were observed among the three groups. Thus, treatment with anti-IL-6 receptor antibody suppressed polyp growth in obese Apc(Min/+) mice fed the high-fat diet. We suggest that IL-6 signaling may be responsible for the obesity-associated colorectal tumorigenesis.</abstract><cop>Japan</cop><pmid>25746084</pmid><doi>10.1620/tjem.235.127</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
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subjects | Adenomatous Polyposis Coli - genetics Animals Antibodies - administration & dosage Antibodies - pharmacology Antibodies - therapeutic use Blood Glucose - metabolism Diet, High-Fat Female Insulin - blood Intestinal Polyps - blood Intestinal Polyps - drug therapy Male Mice, Inbred C57BL Rats Receptors, Interleukin-6 - immunology Triglycerides - blood |
title | Treatment with anti-interleukin-6 receptor antibody ameliorates intestinal polyposis in Apc(Min/+) mice under high-fat diet conditions |
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