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Interleukin-22 ameliorates liver fibrogenesis by attenuating hepatic stellate cell activation and downregulating the levels of inflammatory cytokines
AIM:To investigate the effect of interleukin(IL)-22 onhepatic fibrosis in mice and the possible mechanism involved.METHODS:Liver fibrosis was induced in male BALB/c mice by CCl4.Recombinant IL-22(rm IL-22) was administered intraperitoneally in CCl4-treated mice.Fibrosis was assessed by histology and...
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| Published in: | World journal of gastroenterology : WJG 2015-02, Vol.21 (5), p.1531-1545 |
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| container_title | World journal of gastroenterology : WJG |
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| creator | Lu, Dong-Hong Guo, Xiao-Yun Qin, Shan-Yu Luo, Wei Huang, Xiao-Li Chen, Mei Wang, Jia-Xu Ma, Shi-Jia Yang, Xian-Wen Jiang, Hai-Xing |
| description | AIM:To investigate the effect of interleukin(IL)-22 onhepatic fibrosis in mice and the possible mechanism involved.METHODS:Liver fibrosis was induced in male BALB/c mice by CCl4.Recombinant IL-22(rm IL-22) was administered intraperitoneally in CCl4-treated mice.Fibrosis was assessed by histology and Masson staining.The activation of hepatic stellate cells(HSCs) was investigated by analysis of α-smooth muscle actin expression.The frequencies of T helper(Th) 22 cells,Th17 cells and Th1 cells,the expression of inflammatory cytokines [IL-22,IL-17 A,interferon-γ(IFN-γ),tumor necrosis factor-α(TNF-α),IL-6,IL-1b] and transcription factors [aryl hydrocarbon receptor(AHR),RAR-related orphan receptor(RORγt),T-bet] m RNA in the liver were investigated.In addition,the plasma levels of IL-22,IL-17 A,IFN-γ,TNF-α,IL-6 and IL-1b were evaluated.RESULTS:Significant elevations in circulating Th22 cells,Th17 cells,Th1 cells,IL-22,IL-17 A,and IFN-γ were observed in the hepatic fibrosis group compared with the control group(P < 0.01).Treatment with rm IL-22 in mice with hepatic fibrosis ameliorated the severity of hepatic fibrosis,which was confirmed by lower hepatic fibrosis pathological scores(P < 0.01).Rm IL-22 decreased the frequencies of Th22 cells(6.71% ± 0.97% vs 8.09% ± 0.74%,P < 0.01),Th17 cells(4.34% ± 0.37% vs 5.71% ± 0.24%,P < 0.01),Th1 cells(3.09% ± 0.49% vs 4.91% ± 0.73%,P < 0.01),and the levels of IL-22(56.23 ± 3.08 vs 70.29 ± 3.01,P < 0.01),IL-17A(30.74 ± 2.77 vs 45.68 ± 2.71,P < 0.01),and IFN-γ(74.78 ± 2.61 vs 124.89 ± 2.82,P < 0.01).Down-regulation of IL-22,IL-17 A,IFN-γ,TNF-α,IL-6,IL-1b,AHR RORγt,and T-bet gene expression in the liver was observed in the rm IL-22 group(P < 0.01).CONCLUSION:The frequencies of Th22,Th17 andTh1 cells are elevated in hepatic fibrosis.Rm IL-22 can attenuate HSC activation and down-regulate the levels of inflammatory cytokines,thereby ameliorating liver fibrogenesis. |
| doi_str_mv | 10.3748/wjg.v21.i5.1531 |
| format | article |
| fullrecord | <record><control><sourceid>pubmed_cross</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_4316095</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><cqvip_id>90888889504849534853484956</cqvip_id><sourcerecordid>25663772</sourcerecordid><originalsourceid>FETCH-LOGICAL-c437t-99f89dcdd9a0d25ea84e6751231f46053d3008d41d97d19c7f899a1e679476013</originalsourceid><addsrcrecordid>eNpVkd-OEyEUxonRuHX12jvDC0yXv8NwY2I2rm6yiTd6TehwZsrKQAXaTR_E95Wma6Mk5JzA7_sO4UPoPSVrrsRw8_Q4rw-Mrr1cU8npC7RijOqODYK8RCtKiOo0Z-oKvSnlkRDGuWSv0RWTfc-VYiv0-z5WyAH2P33sGMN2geBTthUKDv4AGU9-k9MMEYoveHPEtlaIe1t9nPEWdq0ZcakQQtPgsVVsx-oP7TxFbKPDLj3FDPM-nDV1CzjAAULBacI-TsEui60pH_F4rKm9A8pb9GqyocC753qNftx9_n77tXv49uX-9tNDNwquaqf1NGg3OqctcUyCHQT0SlLG6SR6IrnjhAxOUKeVo3pUDdeWNkYL1RPKr9HHs-9uv1nAjRBrtsHssl9sPppkvfn_JvqtmdPBCE57omUzuDkbjDmVkmG6aCkxp4RMS8i0hIyX5pRQU3z4d-SF_xtJA_iz5TbF-Vf7sgujyXBaWhIxiDZdDKfdup7_AWpDolo</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype></control><display><type>article</type><title>Interleukin-22 ameliorates liver fibrogenesis by attenuating hepatic stellate cell activation and downregulating the levels of inflammatory cytokines</title><source>Open Access: PubMed Central</source><creator>Lu, Dong-Hong ; Guo, Xiao-Yun ; Qin, Shan-Yu ; Luo, Wei ; Huang, Xiao-Li ; Chen, Mei ; Wang, Jia-Xu ; Ma, Shi-Jia ; Yang, Xian-Wen ; Jiang, Hai-Xing</creator><creatorcontrib>Lu, Dong-Hong ; Guo, Xiao-Yun ; Qin, Shan-Yu ; Luo, Wei ; Huang, Xiao-Li ; Chen, Mei ; Wang, Jia-Xu ; Ma, Shi-Jia ; Yang, Xian-Wen ; Jiang, Hai-Xing</creatorcontrib><description><![CDATA[AIM:To investigate the effect of interleukin(IL)-22 onhepatic fibrosis in mice and the possible mechanism involved.METHODS:Liver fibrosis was induced in male BALB/c mice by CCl4.Recombinant IL-22(rm IL-22) was administered intraperitoneally in CCl4-treated mice.Fibrosis was assessed by histology and Masson staining.The activation of hepatic stellate cells(HSCs) was investigated by analysis of α-smooth muscle actin expression.The frequencies of T helper(Th) 22 cells,Th17 cells and Th1 cells,the expression of inflammatory cytokines [IL-22,IL-17 A,interferon-γ(IFN-γ),tumor necrosis factor-α(TNF-α),IL-6,IL-1b] and transcription factors [aryl hydrocarbon receptor(AHR),RAR-related orphan receptor(RORγt),T-bet] m RNA in the liver were investigated.In addition,the plasma levels of IL-22,IL-17 A,IFN-γ,TNF-α,IL-6 and IL-1b were evaluated.RESULTS:Significant elevations in circulating Th22 cells,Th17 cells,Th1 cells,IL-22,IL-17 A,and IFN-γ were observed in the hepatic fibrosis group compared with the control group(P < 0.01).Treatment with rm IL-22 in mice with hepatic fibrosis ameliorated the severity of hepatic fibrosis,which was confirmed by lower hepatic fibrosis pathological scores(P < 0.01).Rm IL-22 decreased the frequencies of Th22 cells(6.71% ± 0.97% vs 8.09% ± 0.74%,P < 0.01),Th17 cells(4.34% ± 0.37% vs 5.71% ± 0.24%,P < 0.01),Th1 cells(3.09% ± 0.49% vs 4.91% ± 0.73%,P < 0.01),and the levels of IL-22(56.23 ± 3.08 vs 70.29 ± 3.01,P < 0.01),IL-17A(30.74 ± 2.77 vs 45.68 ± 2.71,P < 0.01),and IFN-γ(74.78 ± 2.61 vs 124.89 ± 2.82,P < 0.01).Down-regulation of IL-22,IL-17 A,IFN-γ,TNF-α,IL-6,IL-1b,AHR RORγt,and T-bet gene expression in the liver was observed in the rm IL-22 group(P < 0.01).CONCLUSION:The frequencies of Th22,Th17 andTh1 cells are elevated in hepatic fibrosis.Rm IL-22 can attenuate HSC activation and down-regulate the levels of inflammatory cytokines,thereby ameliorating liver fibrogenesis.]]></description><identifier>ISSN: 1007-9327</identifier><identifier>EISSN: 2219-2840</identifier><identifier>DOI: 10.3748/wjg.v21.i5.1531</identifier><identifier>PMID: 25663772</identifier><language>eng</language><publisher>United States: Baishideng Publishing Group Inc</publisher><subject>Animals ; Anti-Inflammatory Agents - pharmacology ; Basic Study ; Carbon Tetrachloride ; cel ; cells;T ; Cytokines - genetics ; Cytokines - immunology ; Cytokines - metabolism ; helper ; Hepatic Stellate Cells - drug effects ; Hepatic Stellate Cells - immunology ; Hepatic Stellate Cells - metabolism ; Hepatic Stellate Cells - pathology ; Inflammation Mediators - immunology ; Inflammation Mediators - metabolism ; Interleukin-22 ; Interleukins - pharmacology ; Liver - drug effects ; Liver - immunology ; Liver - metabolism ; Liver - pathology ; Liver Cirrhosis, Experimental - chemically induced ; Liver Cirrhosis, Experimental - genetics ; Liver Cirrhosis, Experimental - immunology ; Liver Cirrhosis, Experimental - metabolism ; Liver Cirrhosis, Experimental - pathology ; Liver Cirrhosis, Experimental - prevention & control ; Male ; Mice, Inbred BALB C ; Recombinant Proteins - pharmacology ; RNA, Messenger - metabolism ; Severity of Illness Index ; Signal Transduction - drug effects ; Th1 Cells - drug effects ; Th1 Cells - immunology ; Th1 Cells - metabolism ; Th17 Cells - drug effects ; Th17 Cells - immunology ; Th17 Cells - metabolism ; Time Factors</subject><ispartof>World journal of gastroenterology : WJG, 2015-02, Vol.21 (5), p.1531-1545</ispartof><rights>The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved. 2015</rights><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c437t-99f89dcdd9a0d25ea84e6751231f46053d3008d41d97d19c7f899a1e679476013</citedby><cites>FETCH-LOGICAL-c437t-99f89dcdd9a0d25ea84e6751231f46053d3008d41d97d19c7f899a1e679476013</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Uhttp://image.cqvip.com/vip1000/qk/84123X/84123X.jpg</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4316095/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4316095/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,315,733,786,790,891,27957,27958,53827,53829</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25663772$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Lu, Dong-Hong</creatorcontrib><creatorcontrib>Guo, Xiao-Yun</creatorcontrib><creatorcontrib>Qin, Shan-Yu</creatorcontrib><creatorcontrib>Luo, Wei</creatorcontrib><creatorcontrib>Huang, Xiao-Li</creatorcontrib><creatorcontrib>Chen, Mei</creatorcontrib><creatorcontrib>Wang, Jia-Xu</creatorcontrib><creatorcontrib>Ma, Shi-Jia</creatorcontrib><creatorcontrib>Yang, Xian-Wen</creatorcontrib><creatorcontrib>Jiang, Hai-Xing</creatorcontrib><title>Interleukin-22 ameliorates liver fibrogenesis by attenuating hepatic stellate cell activation and downregulating the levels of inflammatory cytokines</title><title>World journal of gastroenterology : WJG</title><addtitle>World Journal of Gastroenterology</addtitle><description><![CDATA[AIM:To investigate the effect of interleukin(IL)-22 onhepatic fibrosis in mice and the possible mechanism involved.METHODS:Liver fibrosis was induced in male BALB/c mice by CCl4.Recombinant IL-22(rm IL-22) was administered intraperitoneally in CCl4-treated mice.Fibrosis was assessed by histology and Masson staining.The activation of hepatic stellate cells(HSCs) was investigated by analysis of α-smooth muscle actin expression.The frequencies of T helper(Th) 22 cells,Th17 cells and Th1 cells,the expression of inflammatory cytokines [IL-22,IL-17 A,interferon-γ(IFN-γ),tumor necrosis factor-α(TNF-α),IL-6,IL-1b] and transcription factors [aryl hydrocarbon receptor(AHR),RAR-related orphan receptor(RORγt),T-bet] m RNA in the liver were investigated.In addition,the plasma levels of IL-22,IL-17 A,IFN-γ,TNF-α,IL-6 and IL-1b were evaluated.RESULTS:Significant elevations in circulating Th22 cells,Th17 cells,Th1 cells,IL-22,IL-17 A,and IFN-γ were observed in the hepatic fibrosis group compared with the control group(P < 0.01).Treatment with rm IL-22 in mice with hepatic fibrosis ameliorated the severity of hepatic fibrosis,which was confirmed by lower hepatic fibrosis pathological scores(P < 0.01).Rm IL-22 decreased the frequencies of Th22 cells(6.71% ± 0.97% vs 8.09% ± 0.74%,P < 0.01),Th17 cells(4.34% ± 0.37% vs 5.71% ± 0.24%,P < 0.01),Th1 cells(3.09% ± 0.49% vs 4.91% ± 0.73%,P < 0.01),and the levels of IL-22(56.23 ± 3.08 vs 70.29 ± 3.01,P < 0.01),IL-17A(30.74 ± 2.77 vs 45.68 ± 2.71,P < 0.01),and IFN-γ(74.78 ± 2.61 vs 124.89 ± 2.82,P < 0.01).Down-regulation of IL-22,IL-17 A,IFN-γ,TNF-α,IL-6,IL-1b,AHR RORγt,and T-bet gene expression in the liver was observed in the rm IL-22 group(P < 0.01).CONCLUSION:The frequencies of Th22,Th17 andTh1 cells are elevated in hepatic fibrosis.Rm IL-22 can attenuate HSC activation and down-regulate the levels of inflammatory cytokines,thereby ameliorating liver fibrogenesis.]]></description><subject>Animals</subject><subject>Anti-Inflammatory Agents - pharmacology</subject><subject>Basic Study</subject><subject>Carbon Tetrachloride</subject><subject>cel</subject><subject>cells;T</subject><subject>Cytokines - genetics</subject><subject>Cytokines - immunology</subject><subject>Cytokines - metabolism</subject><subject>helper</subject><subject>Hepatic Stellate Cells - drug effects</subject><subject>Hepatic Stellate Cells - immunology</subject><subject>Hepatic Stellate Cells - metabolism</subject><subject>Hepatic Stellate Cells - pathology</subject><subject>Inflammation Mediators - immunology</subject><subject>Inflammation Mediators - metabolism</subject><subject>Interleukin-22</subject><subject>Interleukins - pharmacology</subject><subject>Liver - drug effects</subject><subject>Liver - immunology</subject><subject>Liver - metabolism</subject><subject>Liver - pathology</subject><subject>Liver Cirrhosis, Experimental - chemically induced</subject><subject>Liver Cirrhosis, Experimental - genetics</subject><subject>Liver Cirrhosis, Experimental - immunology</subject><subject>Liver Cirrhosis, Experimental - metabolism</subject><subject>Liver Cirrhosis, Experimental - pathology</subject><subject>Liver Cirrhosis, Experimental - prevention & control</subject><subject>Male</subject><subject>Mice, Inbred BALB C</subject><subject>Recombinant Proteins - pharmacology</subject><subject>RNA, Messenger - metabolism</subject><subject>Severity of Illness Index</subject><subject>Signal Transduction - drug effects</subject><subject>Th1 Cells - drug effects</subject><subject>Th1 Cells - immunology</subject><subject>Th1 Cells - metabolism</subject><subject>Th17 Cells - drug effects</subject><subject>Th17 Cells - immunology</subject><subject>Th17 Cells - metabolism</subject><subject>Time Factors</subject><issn>1007-9327</issn><issn>2219-2840</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><recordid>eNpVkd-OEyEUxonRuHX12jvDC0yXv8NwY2I2rm6yiTd6TehwZsrKQAXaTR_E95Wma6Mk5JzA7_sO4UPoPSVrrsRw8_Q4rw-Mrr1cU8npC7RijOqODYK8RCtKiOo0Z-oKvSnlkRDGuWSv0RWTfc-VYiv0-z5WyAH2P33sGMN2geBTthUKDv4AGU9-k9MMEYoveHPEtlaIe1t9nPEWdq0ZcakQQtPgsVVsx-oP7TxFbKPDLj3FDPM-nDV1CzjAAULBacI-TsEui60pH_F4rKm9A8pb9GqyocC753qNftx9_n77tXv49uX-9tNDNwquaqf1NGg3OqctcUyCHQT0SlLG6SR6IrnjhAxOUKeVo3pUDdeWNkYL1RPKr9HHs-9uv1nAjRBrtsHssl9sPppkvfn_JvqtmdPBCE57omUzuDkbjDmVkmG6aCkxp4RMS8i0hIyX5pRQU3z4d-SF_xtJA_iz5TbF-Vf7sgujyXBaWhIxiDZdDKfdup7_AWpDolo</recordid><startdate>20150207</startdate><enddate>20150207</enddate><creator>Lu, Dong-Hong</creator><creator>Guo, Xiao-Yun</creator><creator>Qin, Shan-Yu</creator><creator>Luo, Wei</creator><creator>Huang, Xiao-Li</creator><creator>Chen, Mei</creator><creator>Wang, Jia-Xu</creator><creator>Ma, Shi-Jia</creator><creator>Yang, Xian-Wen</creator><creator>Jiang, Hai-Xing</creator><general>Baishideng Publishing Group Inc</general><scope>2RA</scope><scope>92L</scope><scope>CQIGP</scope><scope>W91</scope><scope>~WA</scope><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>5PM</scope></search><sort><creationdate>20150207</creationdate><title>Interleukin-22 ameliorates liver fibrogenesis by attenuating hepatic stellate cell activation and downregulating the levels of inflammatory cytokines</title><author>Lu, Dong-Hong ; Guo, Xiao-Yun ; Qin, Shan-Yu ; Luo, Wei ; Huang, Xiao-Li ; Chen, Mei ; Wang, Jia-Xu ; Ma, Shi-Jia ; Yang, Xian-Wen ; Jiang, Hai-Xing</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c437t-99f89dcdd9a0d25ea84e6751231f46053d3008d41d97d19c7f899a1e679476013</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Animals</topic><topic>Anti-Inflammatory Agents - pharmacology</topic><topic>Basic Study</topic><topic>Carbon Tetrachloride</topic><topic>cel</topic><topic>cells;T</topic><topic>Cytokines - genetics</topic><topic>Cytokines - immunology</topic><topic>Cytokines - metabolism</topic><topic>helper</topic><topic>Hepatic Stellate Cells - drug effects</topic><topic>Hepatic Stellate Cells - immunology</topic><topic>Hepatic Stellate Cells - metabolism</topic><topic>Hepatic Stellate Cells - pathology</topic><topic>Inflammation Mediators - immunology</topic><topic>Inflammation Mediators - metabolism</topic><topic>Interleukin-22</topic><topic>Interleukins - pharmacology</topic><topic>Liver - drug effects</topic><topic>Liver - immunology</topic><topic>Liver - metabolism</topic><topic>Liver - pathology</topic><topic>Liver Cirrhosis, Experimental - chemically induced</topic><topic>Liver Cirrhosis, Experimental - genetics</topic><topic>Liver Cirrhosis, Experimental - immunology</topic><topic>Liver Cirrhosis, Experimental - metabolism</topic><topic>Liver Cirrhosis, Experimental - pathology</topic><topic>Liver Cirrhosis, Experimental - prevention & control</topic><topic>Male</topic><topic>Mice, Inbred BALB C</topic><topic>Recombinant Proteins - pharmacology</topic><topic>RNA, Messenger - metabolism</topic><topic>Severity of Illness Index</topic><topic>Signal Transduction - drug effects</topic><topic>Th1 Cells - drug effects</topic><topic>Th1 Cells - immunology</topic><topic>Th1 Cells - metabolism</topic><topic>Th17 Cells - drug effects</topic><topic>Th17 Cells - immunology</topic><topic>Th17 Cells - metabolism</topic><topic>Time Factors</topic><toplevel>online_resources</toplevel><creatorcontrib>Lu, Dong-Hong</creatorcontrib><creatorcontrib>Guo, Xiao-Yun</creatorcontrib><creatorcontrib>Qin, Shan-Yu</creatorcontrib><creatorcontrib>Luo, Wei</creatorcontrib><creatorcontrib>Huang, Xiao-Li</creatorcontrib><creatorcontrib>Chen, Mei</creatorcontrib><creatorcontrib>Wang, Jia-Xu</creatorcontrib><creatorcontrib>Ma, Shi-Jia</creatorcontrib><creatorcontrib>Yang, Xian-Wen</creatorcontrib><creatorcontrib>Jiang, Hai-Xing</creatorcontrib><collection>维普_期刊</collection><collection>中文科技期刊数据库-CALIS站点</collection><collection>维普中文期刊数据库</collection><collection>中文科技期刊数据库-医药卫生</collection><collection>中文科技期刊数据库- 镜像站点</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>World journal of gastroenterology : WJG</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Lu, Dong-Hong</au><au>Guo, Xiao-Yun</au><au>Qin, Shan-Yu</au><au>Luo, Wei</au><au>Huang, Xiao-Li</au><au>Chen, Mei</au><au>Wang, Jia-Xu</au><au>Ma, Shi-Jia</au><au>Yang, Xian-Wen</au><au>Jiang, Hai-Xing</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Interleukin-22 ameliorates liver fibrogenesis by attenuating hepatic stellate cell activation and downregulating the levels of inflammatory cytokines</atitle><jtitle>World journal of gastroenterology : WJG</jtitle><addtitle>World Journal of Gastroenterology</addtitle><date>2015-02-07</date><risdate>2015</risdate><volume>21</volume><issue>5</issue><spage>1531</spage><epage>1545</epage><pages>1531-1545</pages><issn>1007-9327</issn><eissn>2219-2840</eissn><notes><![CDATA[AIM:To investigate the effect of interleukin(IL)-22 onhepatic fibrosis in mice and the possible mechanism involved.METHODS:Liver fibrosis was induced in male BALB/c mice by CCl4.Recombinant IL-22(rm IL-22) was administered intraperitoneally in CCl4-treated mice.Fibrosis was assessed by histology and Masson staining.The activation of hepatic stellate cells(HSCs) was investigated by analysis of α-smooth muscle actin expression.The frequencies of T helper(Th) 22 cells,Th17 cells and Th1 cells,the expression of inflammatory cytokines [IL-22,IL-17 A,interferon-γ(IFN-γ),tumor necrosis factor-α(TNF-α),IL-6,IL-1b] and transcription factors [aryl hydrocarbon receptor(AHR),RAR-related orphan receptor(RORγt),T-bet] m RNA in the liver were investigated.In addition,the plasma levels of IL-22,IL-17 A,IFN-γ,TNF-α,IL-6 and IL-1b were evaluated.RESULTS:Significant elevations in circulating Th22 cells,Th17 cells,Th1 cells,IL-22,IL-17 A,and IFN-γ were observed in the hepatic fibrosis group compared with the control group(P < 0.01).Treatment with rm IL-22 in mice with hepatic fibrosis ameliorated the severity of hepatic fibrosis,which was confirmed by lower hepatic fibrosis pathological scores(P < 0.01).Rm IL-22 decreased the frequencies of Th22 cells(6.71% ± 0.97% vs 8.09% ± 0.74%,P < 0.01),Th17 cells(4.34% ± 0.37% vs 5.71% ± 0.24%,P < 0.01),Th1 cells(3.09% ± 0.49% vs 4.91% ± 0.73%,P < 0.01),and the levels of IL-22(56.23 ± 3.08 vs 70.29 ± 3.01,P < 0.01),IL-17A(30.74 ± 2.77 vs 45.68 ± 2.71,P < 0.01),and IFN-γ(74.78 ± 2.61 vs 124.89 ± 2.82,P < 0.01).Down-regulation of IL-22,IL-17 A,IFN-γ,TNF-α,IL-6,IL-1b,AHR RORγt,and T-bet gene expression in the liver was observed in the rm IL-22 group(P < 0.01).CONCLUSION:The frequencies of Th22,Th17 andTh1 cells are elevated in hepatic fibrosis.Rm IL-22 can attenuate HSC activation and down-regulate the levels of inflammatory cytokines,thereby ameliorating liver fibrogenesis.]]></notes><notes>Dong-Hong Lu;Xiao-Yun Guo;Shan-Yu Qin;Wei Luo;Xiao-Li Huang;Mei Chen;Jia-Xu Wang;Shi-Jia Ma;Xian-Wen Yang;Hai-Xing Jiang;Department of Gastroenterology,The First Affiliated Hospital,Guangxi Medical University</notes><notes>T helper 22 cells;T helper 17 cells;T helper 1 cel</notes><notes>Author contributions: Lu DH, Guo XY, Qin SY, Luo W performed the experiments; Lu DH analyzed the data; Lu DH, Huang XL, Chen M, Wang JX, Ma SJ, Yang XW contributed to the reagents, materials, and analysis tools; Lu DH wrote the paper; Jiang HX designed this experiment.</notes><notes>Correspondence to: Hai-Xing Jiang, PhD, Professor, Department of Gastroenterology, The First Affiliated Hospital, Guangxi Medical University, No. 22, Shuang Yong Road, Nanning 530021, Guangxi Zhuang Autonomous Region, China. jihaxi@163.com</notes><notes>Telephone: +86-771-5356725 Fax: +86-771-5356725</notes><abstract><![CDATA[AIM:To investigate the effect of interleukin(IL)-22 onhepatic fibrosis in mice and the possible mechanism involved.METHODS:Liver fibrosis was induced in male BALB/c mice by CCl4.Recombinant IL-22(rm IL-22) was administered intraperitoneally in CCl4-treated mice.Fibrosis was assessed by histology and Masson staining.The activation of hepatic stellate cells(HSCs) was investigated by analysis of α-smooth muscle actin expression.The frequencies of T helper(Th) 22 cells,Th17 cells and Th1 cells,the expression of inflammatory cytokines [IL-22,IL-17 A,interferon-γ(IFN-γ),tumor necrosis factor-α(TNF-α),IL-6,IL-1b] and transcription factors [aryl hydrocarbon receptor(AHR),RAR-related orphan receptor(RORγt),T-bet] m RNA in the liver were investigated.In addition,the plasma levels of IL-22,IL-17 A,IFN-γ,TNF-α,IL-6 and IL-1b were evaluated.RESULTS:Significant elevations in circulating Th22 cells,Th17 cells,Th1 cells,IL-22,IL-17 A,and IFN-γ were observed in the hepatic fibrosis group compared with the control group(P < 0.01).Treatment with rm IL-22 in mice with hepatic fibrosis ameliorated the severity of hepatic fibrosis,which was confirmed by lower hepatic fibrosis pathological scores(P < 0.01).Rm IL-22 decreased the frequencies of Th22 cells(6.71% ± 0.97% vs 8.09% ± 0.74%,P < 0.01),Th17 cells(4.34% ± 0.37% vs 5.71% ± 0.24%,P < 0.01),Th1 cells(3.09% ± 0.49% vs 4.91% ± 0.73%,P < 0.01),and the levels of IL-22(56.23 ± 3.08 vs 70.29 ± 3.01,P < 0.01),IL-17A(30.74 ± 2.77 vs 45.68 ± 2.71,P < 0.01),and IFN-γ(74.78 ± 2.61 vs 124.89 ± 2.82,P < 0.01).Down-regulation of IL-22,IL-17 A,IFN-γ,TNF-α,IL-6,IL-1b,AHR RORγt,and T-bet gene expression in the liver was observed in the rm IL-22 group(P < 0.01).CONCLUSION:The frequencies of Th22,Th17 andTh1 cells are elevated in hepatic fibrosis.Rm IL-22 can attenuate HSC activation and down-regulate the levels of inflammatory cytokines,thereby ameliorating liver fibrogenesis.]]></abstract><cop>United States</cop><pub>Baishideng Publishing Group Inc</pub><pmid>25663772</pmid><doi>10.3748/wjg.v21.i5.1531</doi><tpages>15</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1007-9327 |
| ispartof | World journal of gastroenterology : WJG, 2015-02, Vol.21 (5), p.1531-1545 |
| issn | 1007-9327 2219-2840 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_4316095 |
| source | Open Access: PubMed Central |
| subjects | Animals Anti-Inflammatory Agents - pharmacology Basic Study Carbon Tetrachloride cel cells T Cytokines - genetics Cytokines - immunology Cytokines - metabolism helper Hepatic Stellate Cells - drug effects Hepatic Stellate Cells - immunology Hepatic Stellate Cells - metabolism Hepatic Stellate Cells - pathology Inflammation Mediators - immunology Inflammation Mediators - metabolism Interleukin-22 Interleukins - pharmacology Liver - drug effects Liver - immunology Liver - metabolism Liver - pathology Liver Cirrhosis, Experimental - chemically induced Liver Cirrhosis, Experimental - genetics Liver Cirrhosis, Experimental - immunology Liver Cirrhosis, Experimental - metabolism Liver Cirrhosis, Experimental - pathology Liver Cirrhosis, Experimental - prevention & control Male Mice, Inbred BALB C Recombinant Proteins - pharmacology RNA, Messenger - metabolism Severity of Illness Index Signal Transduction - drug effects Th1 Cells - drug effects Th1 Cells - immunology Th1 Cells - metabolism Th17 Cells - drug effects Th17 Cells - immunology Th17 Cells - metabolism Time Factors |
| title | Interleukin-22 ameliorates liver fibrogenesis by attenuating hepatic stellate cell activation and downregulating the levels of inflammatory cytokines |
| url | http://sfxeu10.hosted.exlibrisgroup.com/loughborough?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-09-22T02%3A30%3A26IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-pubmed_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Interleukin-22%20ameliorates%20liver%20fibrogenesis%20by%20attenuating%20hepatic%20stellate%20cell%20activation%20and%20downregulating%20the%20levels%20of%20inflammatory%20cytokines&rft.jtitle=World%20journal%20of%20gastroenterology%20:%20WJG&rft.au=Lu,%20Dong-Hong&rft.date=2015-02-07&rft.volume=21&rft.issue=5&rft.spage=1531&rft.epage=1545&rft.pages=1531-1545&rft.issn=1007-9327&rft.eissn=2219-2840&rft_id=info:doi/10.3748/wjg.v21.i5.1531&rft_dat=%3Cpubmed_cross%3E25663772%3C/pubmed_cross%3E%3Cgrp_id%3Ecdi_FETCH-LOGICAL-c437t-99f89dcdd9a0d25ea84e6751231f46053d3008d41d97d19c7f899a1e679476013%3C/grp_id%3E%3Coa%3E%3C/oa%3E%3Curl%3E%3C/url%3E&rft_id=info:oai/&rft_id=info:pmid/25663772&rft_cqvip_id=90888889504849534853484956&rfr_iscdi=true |