The Effect of Antifibrotic Drug Halofugine on Th17 Cells in Concanavalin A‐Induced Liver Fibrosis
Summary Anti‐inflammation strategy is one of the proposed therapeutic approaches to hepatic fibrosis. T helper (Th) 17 cells, which play a detrimental role in experimental murine models of inflammatory diseases, have been demonstrated to participate in the pathogenesis of liver damage. The inhibitor...
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| Veröffentlicht in: | Scandinavian journal of immunology 2014-03, Vol.79 (3), p.163-172 |
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| container_title | Scandinavian journal of immunology |
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| creator | Liang, J. Zhang, B. Shen, R.‐W. Liu, J.‐B. Gao, M.‐H. Geng, X. Li, Y. Li, Y.‐Y. Zhang, W. |
| description | Summary
Anti‐inflammation strategy is one of the proposed therapeutic approaches to hepatic fibrosis. T helper (Th) 17 cells, which play a detrimental role in experimental murine models of inflammatory diseases, have been demonstrated to participate in the pathogenesis of liver damage. The inhibitory effect of halofuginone (HF), an active component of extracts derived from the plant alkaloid febrifugine, on collagen synthesis has been shown in animal models of the fibrotic disease. The aim of this study was to clarify the in vivo effect of HF on Th17 cells in concanavalin A‐induced fibrosis rats. Haematoxylin–eosin (HE) staining and Masson staining were performed to observe collagen deposition. The presence of INF‐gamma, TNF‐alpha, IL‐6, IL‐17, IL‐1beta, IL‐33 and IL‐10 in serum and the presence of ROR‐γt, IL‐17, TGF‐β1 and α‐SMA in liver tissue were detected. Flow cytometry was performed to analyse the percentage of Th17 cells. We observed significantly lower levels of INF‐gamma, TNF‐alpha, IL‐6, IL‐17, IL‐1beta, TGF‐β1 and α‐SMA in HF‐treated group of rats, and the percentage of Th17 cells in splenic lymphocyte was decreased well. Histological examination demonstrated that HF significantly reduced the severity of liver fibrosis in HF‐treated rats. We concluded that HF (10 mg/kg) exerts an antifibrotic impact on Th17 cells and its relative cytokines in rats with ConA‐induced fibrosis. |
| doi_str_mv | 10.1111/sji.12144 |
| format | Article |
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Anti‐inflammation strategy is one of the proposed therapeutic approaches to hepatic fibrosis. T helper (Th) 17 cells, which play a detrimental role in experimental murine models of inflammatory diseases, have been demonstrated to participate in the pathogenesis of liver damage. The inhibitory effect of halofuginone (HF), an active component of extracts derived from the plant alkaloid febrifugine, on collagen synthesis has been shown in animal models of the fibrotic disease. The aim of this study was to clarify the in vivo effect of HF on Th17 cells in concanavalin A‐induced fibrosis rats. Haematoxylin–eosin (HE) staining and Masson staining were performed to observe collagen deposition. The presence of INF‐gamma, TNF‐alpha, IL‐6, IL‐17, IL‐1beta, IL‐33 and IL‐10 in serum and the presence of ROR‐γt, IL‐17, TGF‐β1 and α‐SMA in liver tissue were detected. Flow cytometry was performed to analyse the percentage of Th17 cells. We observed significantly lower levels of INF‐gamma, TNF‐alpha, IL‐6, IL‐17, IL‐1beta, TGF‐β1 and α‐SMA in HF‐treated group of rats, and the percentage of Th17 cells in splenic lymphocyte was decreased well. Histological examination demonstrated that HF significantly reduced the severity of liver fibrosis in HF‐treated rats. We concluded that HF (10 mg/kg) exerts an antifibrotic impact on Th17 cells and its relative cytokines in rats with ConA‐induced fibrosis.</description><identifier>ISSN: 0300-9475</identifier><identifier>EISSN: 1365-3083</identifier><identifier>DOI: 10.1111/sji.12144</identifier><identifier>PMID: 24383550</identifier><language>eng</language><publisher>England: Wiley Subscription Services, Inc</publisher><subject>Actins - metabolism ; Alanine Transaminase - blood ; Albumins - metabolism ; Animals ; Aspartate Aminotransferases - blood ; Cell Differentiation - drug effects ; Cell Differentiation - immunology ; Concanavalin A ; Disease Models, Animal ; Interferon-gamma - blood ; Interleukin-10 - blood ; Interleukin-17 - blood ; Interleukin-17 - metabolism ; Interleukin-1beta - blood ; Interleukin-33 ; Interleukin-6 - blood ; Interleukins - blood ; Liver - drug effects ; Liver - metabolism ; Liver - pathology ; Liver Cirrhosis - chemically induced ; Liver Cirrhosis - drug therapy ; Liver Cirrhosis - immunology ; Male ; Nuclear Receptor Subfamily 1, Group F, Member 3 - metabolism ; Piperidines - therapeutic use ; Protein Synthesis Inhibitors - therapeutic use ; Quinazolinones - therapeutic use ; Rats ; Rats, Wistar ; Th17 Cells - drug effects ; Th17 Cells - immunology ; Transforming Growth Factor beta1 - metabolism ; Tumor Necrosis Factor-alpha - blood</subject><ispartof>Scandinavian journal of immunology, 2014-03, Vol.79 (3), p.163-172</ispartof><rights>2014 John Wiley & Sons Ltd</rights><rights>2014 John Wiley & Sons Ltd.</rights><rights>Copyright © 2014 John Wiley & Sons Ltd</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3884-c79fd7ac4ece5f3f2ff8e33dbdc996c03bad2896626bab11419d50358effcef63</citedby><cites>FETCH-LOGICAL-c3884-c79fd7ac4ece5f3f2ff8e33dbdc996c03bad2896626bab11419d50358effcef63</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1111%2Fsji.12144$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1111%2Fsji.12144$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,778,782,1414,1430,27907,27908,45557,45558,46392,46816</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24383550$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Liang, J.</creatorcontrib><creatorcontrib>Zhang, B.</creatorcontrib><creatorcontrib>Shen, R.‐W.</creatorcontrib><creatorcontrib>Liu, J.‐B.</creatorcontrib><creatorcontrib>Gao, M.‐H.</creatorcontrib><creatorcontrib>Geng, X.</creatorcontrib><creatorcontrib>Li, Y.</creatorcontrib><creatorcontrib>Li, Y.‐Y.</creatorcontrib><creatorcontrib>Zhang, W.</creatorcontrib><title>The Effect of Antifibrotic Drug Halofugine on Th17 Cells in Concanavalin A‐Induced Liver Fibrosis</title><title>Scandinavian journal of immunology</title><addtitle>Scand J Immunol</addtitle><description>Summary
Anti‐inflammation strategy is one of the proposed therapeutic approaches to hepatic fibrosis. T helper (Th) 17 cells, which play a detrimental role in experimental murine models of inflammatory diseases, have been demonstrated to participate in the pathogenesis of liver damage. The inhibitory effect of halofuginone (HF), an active component of extracts derived from the plant alkaloid febrifugine, on collagen synthesis has been shown in animal models of the fibrotic disease. The aim of this study was to clarify the in vivo effect of HF on Th17 cells in concanavalin A‐induced fibrosis rats. Haematoxylin–eosin (HE) staining and Masson staining were performed to observe collagen deposition. The presence of INF‐gamma, TNF‐alpha, IL‐6, IL‐17, IL‐1beta, IL‐33 and IL‐10 in serum and the presence of ROR‐γt, IL‐17, TGF‐β1 and α‐SMA in liver tissue were detected. Flow cytometry was performed to analyse the percentage of Th17 cells. We observed significantly lower levels of INF‐gamma, TNF‐alpha, IL‐6, IL‐17, IL‐1beta, TGF‐β1 and α‐SMA in HF‐treated group of rats, and the percentage of Th17 cells in splenic lymphocyte was decreased well. Histological examination demonstrated that HF significantly reduced the severity of liver fibrosis in HF‐treated rats. We concluded that HF (10 mg/kg) exerts an antifibrotic impact on Th17 cells and its relative cytokines in rats with ConA‐induced fibrosis.</description><subject>Actins - metabolism</subject><subject>Alanine Transaminase - blood</subject><subject>Albumins - metabolism</subject><subject>Animals</subject><subject>Aspartate Aminotransferases - blood</subject><subject>Cell Differentiation - drug effects</subject><subject>Cell Differentiation - immunology</subject><subject>Concanavalin A</subject><subject>Disease Models, Animal</subject><subject>Interferon-gamma - blood</subject><subject>Interleukin-10 - blood</subject><subject>Interleukin-17 - blood</subject><subject>Interleukin-17 - metabolism</subject><subject>Interleukin-1beta - blood</subject><subject>Interleukin-33</subject><subject>Interleukin-6 - blood</subject><subject>Interleukins - blood</subject><subject>Liver - drug effects</subject><subject>Liver - metabolism</subject><subject>Liver - pathology</subject><subject>Liver Cirrhosis - chemically induced</subject><subject>Liver Cirrhosis - drug therapy</subject><subject>Liver Cirrhosis - immunology</subject><subject>Male</subject><subject>Nuclear Receptor Subfamily 1, Group F, Member 3 - metabolism</subject><subject>Piperidines - therapeutic use</subject><subject>Protein Synthesis Inhibitors - therapeutic use</subject><subject>Quinazolinones - therapeutic use</subject><subject>Rats</subject><subject>Rats, Wistar</subject><subject>Th17 Cells - drug effects</subject><subject>Th17 Cells - immunology</subject><subject>Transforming Growth Factor beta1 - metabolism</subject><subject>Tumor Necrosis Factor-alpha - blood</subject><issn>0300-9475</issn><issn>1365-3083</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kMtKAzEUhoMotl4WvoAE3OhiNNe5LEtttVJwYV0PmcxJmzLN1Emn0p2P4DP6JKZWXQiezeHAx8d_foTOKLmmYW783F5TRoXYQ13KYxlxkvJ91CWckCgTieygI-_nhFDOEn6IOkzwlEtJukhPZoAHxoBe4drgnltZY4umXlmNb5t2iu9VVZt2ah3g2uHJjCa4D1XlsXW4XzutnFqrKhy9j7f3kStbDSUe2zU0eLgVeetP0IFRlYfT732MnoeDSf8-Gj_ejfq9caR5mopIJ5kpE6UFaJCGG2ZMCpyXRamzLNaEF6pkaRbHLC5UQamgWSkJlykYo8HE_Bhd7rzLpn5pwa_yhfU6hFUO6tbnVBIhJKExC-jFH3Ret40L6bYUFQlj8VZ4taN0-MM3YPJlYxeq2eSU5Nvm89B8_tV8YM-_jW2xgPKX_Kk6ADc74NVWsPnflD89jHbKT3FmjQw</recordid><startdate>201403</startdate><enddate>201403</enddate><creator>Liang, J.</creator><creator>Zhang, B.</creator><creator>Shen, R.‐W.</creator><creator>Liu, J.‐B.</creator><creator>Gao, M.‐H.</creator><creator>Geng, X.</creator><creator>Li, Y.</creator><creator>Li, Y.‐Y.</creator><creator>Zhang, W.</creator><general>Wiley Subscription Services, Inc</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>7QP</scope><scope>7QR</scope><scope>7T5</scope><scope>7TK</scope><scope>7U9</scope><scope>8FD</scope><scope>FR3</scope><scope>H94</scope><scope>K9.</scope><scope>M7N</scope><scope>NAPCQ</scope><scope>P64</scope><scope>7X8</scope></search><sort><creationdate>201403</creationdate><title>The Effect of Antifibrotic Drug Halofugine on Th17 Cells in Concanavalin A‐Induced Liver Fibrosis</title><author>Liang, J. ; 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Anti‐inflammation strategy is one of the proposed therapeutic approaches to hepatic fibrosis. T helper (Th) 17 cells, which play a detrimental role in experimental murine models of inflammatory diseases, have been demonstrated to participate in the pathogenesis of liver damage. The inhibitory effect of halofuginone (HF), an active component of extracts derived from the plant alkaloid febrifugine, on collagen synthesis has been shown in animal models of the fibrotic disease. The aim of this study was to clarify the in vivo effect of HF on Th17 cells in concanavalin A‐induced fibrosis rats. Haematoxylin–eosin (HE) staining and Masson staining were performed to observe collagen deposition. The presence of INF‐gamma, TNF‐alpha, IL‐6, IL‐17, IL‐1beta, IL‐33 and IL‐10 in serum and the presence of ROR‐γt, IL‐17, TGF‐β1 and α‐SMA in liver tissue were detected. Flow cytometry was performed to analyse the percentage of Th17 cells. We observed significantly lower levels of INF‐gamma, TNF‐alpha, IL‐6, IL‐17, IL‐1beta, TGF‐β1 and α‐SMA in HF‐treated group of rats, and the percentage of Th17 cells in splenic lymphocyte was decreased well. Histological examination demonstrated that HF significantly reduced the severity of liver fibrosis in HF‐treated rats. We concluded that HF (10 mg/kg) exerts an antifibrotic impact on Th17 cells and its relative cytokines in rats with ConA‐induced fibrosis.</abstract><cop>England</cop><pub>Wiley Subscription Services, Inc</pub><pmid>24383550</pmid><doi>10.1111/sji.12144</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Actins - metabolism Alanine Transaminase - blood Albumins - metabolism Animals Aspartate Aminotransferases - blood Cell Differentiation - drug effects Cell Differentiation - immunology Concanavalin A Disease Models, Animal Interferon-gamma - blood Interleukin-10 - blood Interleukin-17 - blood Interleukin-17 - metabolism Interleukin-1beta - blood Interleukin-33 Interleukin-6 - blood Interleukins - blood Liver - drug effects Liver - metabolism Liver - pathology Liver Cirrhosis - chemically induced Liver Cirrhosis - drug therapy Liver Cirrhosis - immunology Male Nuclear Receptor Subfamily 1, Group F, Member 3 - metabolism Piperidines - therapeutic use Protein Synthesis Inhibitors - therapeutic use Quinazolinones - therapeutic use Rats Rats, Wistar Th17 Cells - drug effects Th17 Cells - immunology Transforming Growth Factor beta1 - metabolism Tumor Necrosis Factor-alpha - blood |
| title | The Effect of Antifibrotic Drug Halofugine on Th17 Cells in Concanavalin A‐Induced Liver Fibrosis |
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