Hepatic Macrophages Express Melanoma Differentiation-Associated Gene 5 in Nonalcoholic Steatohepatitis
The activation of innate immune system is essential for the pathogenesis of nonalcoholic steatohepatitis (NASH). Among pattern recognition receptors, it is well-characterized that toll-like receptors (TLRs) are deeply involved in the development of NASH to reflect exposure of the liver to gut-driven...
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| Veröffentlicht in: | Inflammation 2022-02, Vol.45 (1), p.343-355 |
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| creator | Kawaguchi, Shogo Sakuraba, Hirotake Horiuchi, Momone Ding, Jiangli Matsumiya, Tomoh Seya, Kazuhiko Iino, Chikara Endo, Tetsu Kikuchi, Hidezumi Yoshida, Shukuko Hiraga, Hiroto Fukuda, Shinsaku Imaizumi, Tadaatsu |
| description | The activation of innate immune system is essential for the pathogenesis of nonalcoholic steatohepatitis (NASH). Among pattern recognition receptors, it is well-characterized that toll-like receptors (TLRs) are deeply involved in the development of NASH to reflect exposure of the liver to gut-driven endotoxins. In contrast, it has not been elucidated whether retinoic acid-inducible gene-I (RIG-I)-like receptors (RLRs) are similarly implicated in the disease progression. In the present study, we examined the expression of melanoma differentiation-associated antigen 5 (MDA5), known to be a member of RLRs, in a diet-induced murine model of NASH. The liver tissues were collected from C57BL/6 J mice at 1, 3, and 6 weeks after choline-deficient
l
-amino acid-defined high-fat diet (CDAHFD), and the expression of MDA5 was analyzed by western blotting, immunofluorescence (IF), and real-time quantitative PCR (qPCR). The results of western blotting showed that hepatic expression of MDA5 was increased at 3 and 6 weeks. In IF, MDA5-positive cells co-expressed F4/80 and CD11b, indicating they were activated macrophages, and these cells began to appear at 1 week after CDAHFD. The mRNA expression of MDA5 was significantly upregulated at 1 week. Additionally, we performed IF using liver biopsy specimens collected from 11 patients with nonalcoholic fatty liver diseases (NAFLD), and found that MDA5-positive macrophages were detected in eight out of eleven patients. In an in vitro study, MDA5 was induced upon stimulation with lipopolysaccharide in murine bone marrow-derived macrophages and THP-1 cells. Our findings suggest that MDA5 may be involved in the inflammation of NASH. |
| doi_str_mv | 10.1007/s10753-021-01550-8 |
| format | Article |
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l
-amino acid-defined high-fat diet (CDAHFD), and the expression of MDA5 was analyzed by western blotting, immunofluorescence (IF), and real-time quantitative PCR (qPCR). The results of western blotting showed that hepatic expression of MDA5 was increased at 3 and 6 weeks. In IF, MDA5-positive cells co-expressed F4/80 and CD11b, indicating they were activated macrophages, and these cells began to appear at 1 week after CDAHFD. The mRNA expression of MDA5 was significantly upregulated at 1 week. Additionally, we performed IF using liver biopsy specimens collected from 11 patients with nonalcoholic fatty liver diseases (NAFLD), and found that MDA5-positive macrophages were detected in eight out of eleven patients. In an in vitro study, MDA5 was induced upon stimulation with lipopolysaccharide in murine bone marrow-derived macrophages and THP-1 cells. Our findings suggest that MDA5 may be involved in the inflammation of NASH.</description><identifier>ISSN: 0360-3997</identifier><identifier>ISSN: 1573-2576</identifier><identifier>EISSN: 1573-2576</identifier><identifier>DOI: 10.1007/s10753-021-01550-8</identifier><identifier>PMID: 34523053</identifier><language>eng</language><publisher>New York: Springer US</publisher><subject>Adult ; Aged ; Amino acids ; Animal models ; Animals ; Biomarkers - metabolism ; Biomedical and Life Sciences ; Biomedicine ; Biopsy ; Bone marrow ; CD11b antigen ; Endotoxins ; Fatty liver ; Female ; Gene expression ; High fat diet ; Humans ; Immune system ; Immunofluorescence ; Immunology ; Innate immunity ; Interferon-Induced Helicase, IFIH1 - metabolism ; Internal Medicine ; Lipopolysaccharides ; Liver ; Liver - immunology ; Liver - metabolism ; Liver diseases ; Macrophages ; Macrophages - metabolism ; Male ; Melanoma ; Mice ; Mice, Inbred C57BL ; Middle Aged ; Non-alcoholic Fatty Liver Disease - immunology ; Non-alcoholic Fatty Liver Disease - metabolism ; Original Article ; Pathology ; Pattern recognition receptors ; Pharmacology/Toxicology ; Retinoic acid ; Rheumatology ; THP-1 Cells ; Toll-like receptors ; Western blotting</subject><ispartof>Inflammation, 2022-02, Vol.45 (1), p.343-355</ispartof><rights>The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2021</rights><rights>2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.</rights><rights>The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2021.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c485t-a0e29c525bc4f7e91a1faf9fa92ef997006b08504370b0eb3cc47a1546376b6b3</citedby><cites>FETCH-LOGICAL-c485t-a0e29c525bc4f7e91a1faf9fa92ef997006b08504370b0eb3cc47a1546376b6b3</cites><orcidid>0000-0001-5599-1110</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s10753-021-01550-8$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s10753-021-01550-8$$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/34523053$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kawaguchi, Shogo</creatorcontrib><creatorcontrib>Sakuraba, Hirotake</creatorcontrib><creatorcontrib>Horiuchi, Momone</creatorcontrib><creatorcontrib>Ding, Jiangli</creatorcontrib><creatorcontrib>Matsumiya, Tomoh</creatorcontrib><creatorcontrib>Seya, Kazuhiko</creatorcontrib><creatorcontrib>Iino, Chikara</creatorcontrib><creatorcontrib>Endo, Tetsu</creatorcontrib><creatorcontrib>Kikuchi, Hidezumi</creatorcontrib><creatorcontrib>Yoshida, Shukuko</creatorcontrib><creatorcontrib>Hiraga, Hiroto</creatorcontrib><creatorcontrib>Fukuda, Shinsaku</creatorcontrib><creatorcontrib>Imaizumi, Tadaatsu</creatorcontrib><title>Hepatic Macrophages Express Melanoma Differentiation-Associated Gene 5 in Nonalcoholic Steatohepatitis</title><title>Inflammation</title><addtitle>Inflammation</addtitle><addtitle>Inflammation</addtitle><description>The activation of innate immune system is essential for the pathogenesis of nonalcoholic steatohepatitis (NASH). Among pattern recognition receptors, it is well-characterized that toll-like receptors (TLRs) are deeply involved in the development of NASH to reflect exposure of the liver to gut-driven endotoxins. In contrast, it has not been elucidated whether retinoic acid-inducible gene-I (RIG-I)-like receptors (RLRs) are similarly implicated in the disease progression. In the present study, we examined the expression of melanoma differentiation-associated antigen 5 (MDA5), known to be a member of RLRs, in a diet-induced murine model of NASH. The liver tissues were collected from C57BL/6 J mice at 1, 3, and 6 weeks after choline-deficient
l
-amino acid-defined high-fat diet (CDAHFD), and the expression of MDA5 was analyzed by western blotting, immunofluorescence (IF), and real-time quantitative PCR (qPCR). The results of western blotting showed that hepatic expression of MDA5 was increased at 3 and 6 weeks. In IF, MDA5-positive cells co-expressed F4/80 and CD11b, indicating they were activated macrophages, and these cells began to appear at 1 week after CDAHFD. The mRNA expression of MDA5 was significantly upregulated at 1 week. Additionally, we performed IF using liver biopsy specimens collected from 11 patients with nonalcoholic fatty liver diseases (NAFLD), and found that MDA5-positive macrophages were detected in eight out of eleven patients. In an in vitro study, MDA5 was induced upon stimulation with lipopolysaccharide in murine bone marrow-derived macrophages and THP-1 cells. Our findings suggest that MDA5 may be involved in the inflammation of NASH.</description><subject>Adult</subject><subject>Aged</subject><subject>Amino acids</subject><subject>Animal models</subject><subject>Animals</subject><subject>Biomarkers - metabolism</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Biopsy</subject><subject>Bone marrow</subject><subject>CD11b antigen</subject><subject>Endotoxins</subject><subject>Fatty liver</subject><subject>Female</subject><subject>Gene expression</subject><subject>High fat diet</subject><subject>Humans</subject><subject>Immune system</subject><subject>Immunofluorescence</subject><subject>Immunology</subject><subject>Innate immunity</subject><subject>Interferon-Induced Helicase, IFIH1 - metabolism</subject><subject>Internal Medicine</subject><subject>Lipopolysaccharides</subject><subject>Liver</subject><subject>Liver - immunology</subject><subject>Liver - metabolism</subject><subject>Liver diseases</subject><subject>Macrophages</subject><subject>Macrophages - metabolism</subject><subject>Male</subject><subject>Melanoma</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Middle Aged</subject><subject>Non-alcoholic Fatty Liver Disease - immunology</subject><subject>Non-alcoholic Fatty Liver Disease - metabolism</subject><subject>Original Article</subject><subject>Pathology</subject><subject>Pattern recognition receptors</subject><subject>Pharmacology/Toxicology</subject><subject>Retinoic acid</subject><subject>Rheumatology</subject><subject>THP-1 Cells</subject><subject>Toll-like receptors</subject><subject>Western blotting</subject><issn>0360-3997</issn><issn>1573-2576</issn><issn>1573-2576</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNp9kUtPxCAUhYnR6Dj6B1yYJm7coBcopV0aH6OJj4W6JpS5ODWdUqGT6L8XZ0ZNXLiChO8e7jmHkAMGJwxAnUYGSgoKnFFgUgItN8iISSUol6rYJCMQBVBRVWqH7Mb4CgBlVYptsiNyyQVIMSLuGnszNDa7Mzb4fmZeMGaX733AGLM7bE3n5ya7aJzDgN3QJNZ39CxGb9Mdp9kEO8xk1nTZve9Ma_3Mt0nucUAz-NlSfGjiHtlypo24vz7H5Pnq8un8mt4-TG7Oz26pzUs5UAPIKyu5rG3uFFbMMGdc5UzF0SUfAEUNpYRcKKgBa2FtrgyTeSFUURe1GJPjlW4f_NsC46DnTbTYJh_oF1GnYHglypyphB79QV_9IiQLiSp4DiKtwRPFV1RKJ8aATvehmZvwoRnorxb0qgWdWtDLFnSZhg7X0ot6jtOfke_YEyBWQExP3QuG37__kf0E0JuSbQ</recordid><startdate>20220201</startdate><enddate>20220201</enddate><creator>Kawaguchi, Shogo</creator><creator>Sakuraba, Hirotake</creator><creator>Horiuchi, Momone</creator><creator>Ding, Jiangli</creator><creator>Matsumiya, Tomoh</creator><creator>Seya, Kazuhiko</creator><creator>Iino, Chikara</creator><creator>Endo, Tetsu</creator><creator>Kikuchi, Hidezumi</creator><creator>Yoshida, Shukuko</creator><creator>Hiraga, Hiroto</creator><creator>Fukuda, Shinsaku</creator><creator>Imaizumi, Tadaatsu</creator><general>Springer US</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>7T5</scope><scope>7TO</scope><scope>7U9</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>BENPR</scope><scope>CCPQU</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>H94</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>PHGZM</scope><scope>PHGZT</scope><scope>PJZUB</scope><scope>PKEHL</scope><scope>PPXIY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0001-5599-1110</orcidid></search><sort><creationdate>20220201</creationdate><title>Hepatic Macrophages Express Melanoma Differentiation-Associated Gene 5 in Nonalcoholic Steatohepatitis</title><author>Kawaguchi, Shogo ; Sakuraba, Hirotake ; Horiuchi, Momone ; Ding, Jiangli ; Matsumiya, Tomoh ; Seya, Kazuhiko ; Iino, Chikara ; Endo, Tetsu ; Kikuchi, Hidezumi ; Yoshida, Shukuko ; Hiraga, Hiroto ; Fukuda, Shinsaku ; Imaizumi, Tadaatsu</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c485t-a0e29c525bc4f7e91a1faf9fa92ef997006b08504370b0eb3cc47a1546376b6b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2022</creationdate><topic>Adult</topic><topic>Aged</topic><topic>Amino acids</topic><topic>Animal models</topic><topic>Animals</topic><topic>Biomarkers - metabolism</topic><topic>Biomedical and Life Sciences</topic><topic>Biomedicine</topic><topic>Biopsy</topic><topic>Bone marrow</topic><topic>CD11b antigen</topic><topic>Endotoxins</topic><topic>Fatty liver</topic><topic>Female</topic><topic>Gene expression</topic><topic>High fat diet</topic><topic>Humans</topic><topic>Immune system</topic><topic>Immunofluorescence</topic><topic>Immunology</topic><topic>Innate immunity</topic><topic>Interferon-Induced Helicase, IFIH1 - metabolism</topic><topic>Internal Medicine</topic><topic>Lipopolysaccharides</topic><topic>Liver</topic><topic>Liver - immunology</topic><topic>Liver - metabolism</topic><topic>Liver diseases</topic><topic>Macrophages</topic><topic>Macrophages - metabolism</topic><topic>Male</topic><topic>Melanoma</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Middle Aged</topic><topic>Non-alcoholic Fatty Liver Disease - immunology</topic><topic>Non-alcoholic Fatty Liver Disease - metabolism</topic><topic>Original Article</topic><topic>Pathology</topic><topic>Pattern recognition receptors</topic><topic>Pharmacology/Toxicology</topic><topic>Retinoic acid</topic><topic>Rheumatology</topic><topic>THP-1 Cells</topic><topic>Toll-like receptors</topic><topic>Western blotting</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kawaguchi, Shogo</creatorcontrib><creatorcontrib>Sakuraba, Hirotake</creatorcontrib><creatorcontrib>Horiuchi, Momone</creatorcontrib><creatorcontrib>Ding, Jiangli</creatorcontrib><creatorcontrib>Matsumiya, Tomoh</creatorcontrib><creatorcontrib>Seya, Kazuhiko</creatorcontrib><creatorcontrib>Iino, Chikara</creatorcontrib><creatorcontrib>Endo, Tetsu</creatorcontrib><creatorcontrib>Kikuchi, Hidezumi</creatorcontrib><creatorcontrib>Yoshida, Shukuko</creatorcontrib><creatorcontrib>Hiraga, Hiroto</creatorcontrib><creatorcontrib>Fukuda, Shinsaku</creatorcontrib><creatorcontrib>Imaizumi, Tadaatsu</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>Immunology Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Virology and AIDS 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</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>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>ProQuest Central (New)</collection><collection>ProQuest One Academic (New)</collection><collection>ProQuest Health & Medical Research Collection</collection><collection>ProQuest One Academic Middle East (New)</collection><collection>ProQuest One Health & Nursing</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><collection>MEDLINE - Academic</collection><jtitle>Inflammation</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kawaguchi, Shogo</au><au>Sakuraba, Hirotake</au><au>Horiuchi, Momone</au><au>Ding, Jiangli</au><au>Matsumiya, Tomoh</au><au>Seya, Kazuhiko</au><au>Iino, Chikara</au><au>Endo, Tetsu</au><au>Kikuchi, Hidezumi</au><au>Yoshida, Shukuko</au><au>Hiraga, Hiroto</au><au>Fukuda, Shinsaku</au><au>Imaizumi, Tadaatsu</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Hepatic Macrophages Express Melanoma Differentiation-Associated Gene 5 in Nonalcoholic Steatohepatitis</atitle><jtitle>Inflammation</jtitle><stitle>Inflammation</stitle><addtitle>Inflammation</addtitle><date>2022-02-01</date><risdate>2022</risdate><volume>45</volume><issue>1</issue><spage>343</spage><epage>355</epage><pages>343-355</pages><issn>0360-3997</issn><issn>1573-2576</issn><eissn>1573-2576</eissn><abstract>The activation of innate immune system is essential for the pathogenesis of nonalcoholic steatohepatitis (NASH). Among pattern recognition receptors, it is well-characterized that toll-like receptors (TLRs) are deeply involved in the development of NASH to reflect exposure of the liver to gut-driven endotoxins. In contrast, it has not been elucidated whether retinoic acid-inducible gene-I (RIG-I)-like receptors (RLRs) are similarly implicated in the disease progression. In the present study, we examined the expression of melanoma differentiation-associated antigen 5 (MDA5), known to be a member of RLRs, in a diet-induced murine model of NASH. The liver tissues were collected from C57BL/6 J mice at 1, 3, and 6 weeks after choline-deficient
l
-amino acid-defined high-fat diet (CDAHFD), and the expression of MDA5 was analyzed by western blotting, immunofluorescence (IF), and real-time quantitative PCR (qPCR). The results of western blotting showed that hepatic expression of MDA5 was increased at 3 and 6 weeks. In IF, MDA5-positive cells co-expressed F4/80 and CD11b, indicating they were activated macrophages, and these cells began to appear at 1 week after CDAHFD. The mRNA expression of MDA5 was significantly upregulated at 1 week. Additionally, we performed IF using liver biopsy specimens collected from 11 patients with nonalcoholic fatty liver diseases (NAFLD), and found that MDA5-positive macrophages were detected in eight out of eleven patients. In an in vitro study, MDA5 was induced upon stimulation with lipopolysaccharide in murine bone marrow-derived macrophages and THP-1 cells. Our findings suggest that MDA5 may be involved in the inflammation of NASH.</abstract><cop>New York</cop><pub>Springer US</pub><pmid>34523053</pmid><doi>10.1007/s10753-021-01550-8</doi><tpages>13</tpages><orcidid>https://orcid.org/0000-0001-5599-1110</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | Adult Aged Amino acids Animal models Animals Biomarkers - metabolism Biomedical and Life Sciences Biomedicine Biopsy Bone marrow CD11b antigen Endotoxins Fatty liver Female Gene expression High fat diet Humans Immune system Immunofluorescence Immunology Innate immunity Interferon-Induced Helicase, IFIH1 - metabolism Internal Medicine Lipopolysaccharides Liver Liver - immunology Liver - metabolism Liver diseases Macrophages Macrophages - metabolism Male Melanoma Mice Mice, Inbred C57BL Middle Aged Non-alcoholic Fatty Liver Disease - immunology Non-alcoholic Fatty Liver Disease - metabolism Original Article Pathology Pattern recognition receptors Pharmacology/Toxicology Retinoic acid Rheumatology THP-1 Cells Toll-like receptors Western blotting |
| title | Hepatic Macrophages Express Melanoma Differentiation-Associated Gene 5 in Nonalcoholic Steatohepatitis |
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