Expression of suppressors of cytokine signaling during liver regeneration
The cytokines TNF and IL-6 play a critical role early in liver regeneration following partial hepatectomy (PH). Since IL-6 activates signal transducers and activators of transcription (STATs), we examined whether the suppressors of cytokine signaling (SOCS) may be involved in terminating IL-6 signal...
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| Veröffentlicht in: | The Journal of clinical investigation 2001-05, Vol.107 (10), p.1285-1292 |
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| creator | Campbell, J S Prichard, L Schaper, F Schmitz, J Stephenson-Famy, A Rosenfeld, M E Argast, G M Heinrich, P C Fausto, N |
| description | The cytokines TNF and IL-6 play a critical role early in liver regeneration following partial hepatectomy (PH). Since IL-6 activates signal transducers and activators of transcription (STATs), we examined whether the suppressors of cytokine signaling (SOCS) may be involved in terminating IL-6 signaling. We show here that SOCS-3 mRNA is induced 40-fold 2 hours after surgery. SOCS-2 and CIS mRNA are only weakly induced, and SOCS-1 is not detectable. SOCS-3 induction after PH is transient and correlates with a decrease in STAT-3 DNA binding and a loss of tyrosine 705 phosphorylation. This response is markedly reduced in IL-6 knockout (KO) mice. TNF injection induces SOCS-3 mRNA in wild-type mice (albeit weakly compared with the increase observed after PH) but not in TNF receptor 1 or IL-6 KO mice. In contrast, IL-6 injection induces SOCS-3 in these animals, demonstrating a requirement for IL-6 in SOCS-3 induction. IL-6 injection into wild-type mice also induces SOCS-1, -2, and CIS mRNA, in addition to SOCS-3. Together, these results suggest that SOCS-3 may be a key component in downregulating STAT-3 signaling after PH and that SOCS-3 mRNA levels in the regenerating liver are regulated by IL-6. |
| doi_str_mv | 10.1172/jci11867 |
| format | Article |
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Since IL-6 activates signal transducers and activators of transcription (STATs), we examined whether the suppressors of cytokine signaling (SOCS) may be involved in terminating IL-6 signaling. We show here that SOCS-3 mRNA is induced 40-fold 2 hours after surgery. SOCS-2 and CIS mRNA are only weakly induced, and SOCS-1 is not detectable. SOCS-3 induction after PH is transient and correlates with a decrease in STAT-3 DNA binding and a loss of tyrosine 705 phosphorylation. This response is markedly reduced in IL-6 knockout (KO) mice. TNF injection induces SOCS-3 mRNA in wild-type mice (albeit weakly compared with the increase observed after PH) but not in TNF receptor 1 or IL-6 KO mice. In contrast, IL-6 injection induces SOCS-3 in these animals, demonstrating a requirement for IL-6 in SOCS-3 induction. IL-6 injection into wild-type mice also induces SOCS-1, -2, and CIS mRNA, in addition to SOCS-3. Together, these results suggest that SOCS-3 may be a key component in downregulating STAT-3 signaling after PH and that SOCS-3 mRNA levels in the regenerating liver are regulated by IL-6.</description><identifier>ISSN: 0021-9738</identifier><identifier>DOI: 10.1172/jci11867</identifier><identifier>PMID: 11375418</identifier><language>eng</language><publisher>United States: American Society for Clinical Investigation</publisher><subject>Animals ; Antigens, CD - genetics ; DNA-Binding Proteins - metabolism ; Gene Expression Regulation ; Hepatectomy ; Interleukin-6 - immunology ; Liver Regeneration - immunology ; Mice ; Mice, Knockout ; Proteins - genetics ; Receptors, Tumor Necrosis Factor - genetics ; Receptors, Tumor Necrosis Factor, Type I ; Repressor Proteins ; Signal Transduction ; STAT3 Transcription Factor ; Suppressor of Cytokine Signaling 3 Protein ; Suppressor of Cytokine Signaling Proteins ; Trans-Activators - metabolism ; Transcription Factors ; Tumor Necrosis Factor-alpha - immunology</subject><ispartof>The Journal of clinical investigation, 2001-05, Vol.107 (10), p.1285-1292</ispartof><rights>Copyright © 2001, American Society for Clinical Investigation 2001</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c433t-43c4a9ac491623e432c61e99850b6c7fa351ca28b59c4cba25bd894230faf6983</citedby><cites>FETCH-LOGICAL-c433t-43c4a9ac491623e432c61e99850b6c7fa351ca28b59c4cba25bd894230faf6983</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC209297/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC209297/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,723,776,780,881,27903,27904,53770,53772</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/11375418$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Campbell, J S</creatorcontrib><creatorcontrib>Prichard, L</creatorcontrib><creatorcontrib>Schaper, F</creatorcontrib><creatorcontrib>Schmitz, J</creatorcontrib><creatorcontrib>Stephenson-Famy, A</creatorcontrib><creatorcontrib>Rosenfeld, M E</creatorcontrib><creatorcontrib>Argast, G M</creatorcontrib><creatorcontrib>Heinrich, P C</creatorcontrib><creatorcontrib>Fausto, N</creatorcontrib><title>Expression of suppressors of cytokine signaling during liver regeneration</title><title>The Journal of clinical investigation</title><addtitle>J Clin Invest</addtitle><description>The cytokines TNF and IL-6 play a critical role early in liver regeneration following partial hepatectomy (PH). Since IL-6 activates signal transducers and activators of transcription (STATs), we examined whether the suppressors of cytokine signaling (SOCS) may be involved in terminating IL-6 signaling. We show here that SOCS-3 mRNA is induced 40-fold 2 hours after surgery. SOCS-2 and CIS mRNA are only weakly induced, and SOCS-1 is not detectable. SOCS-3 induction after PH is transient and correlates with a decrease in STAT-3 DNA binding and a loss of tyrosine 705 phosphorylation. This response is markedly reduced in IL-6 knockout (KO) mice. TNF injection induces SOCS-3 mRNA in wild-type mice (albeit weakly compared with the increase observed after PH) but not in TNF receptor 1 or IL-6 KO mice. In contrast, IL-6 injection induces SOCS-3 in these animals, demonstrating a requirement for IL-6 in SOCS-3 induction. IL-6 injection into wild-type mice also induces SOCS-1, -2, and CIS mRNA, in addition to SOCS-3. Together, these results suggest that SOCS-3 may be a key component in downregulating STAT-3 signaling after PH and that SOCS-3 mRNA levels in the regenerating liver are regulated by IL-6.</description><subject>Animals</subject><subject>Antigens, CD - genetics</subject><subject>DNA-Binding Proteins - metabolism</subject><subject>Gene Expression Regulation</subject><subject>Hepatectomy</subject><subject>Interleukin-6 - immunology</subject><subject>Liver Regeneration - immunology</subject><subject>Mice</subject><subject>Mice, Knockout</subject><subject>Proteins - genetics</subject><subject>Receptors, Tumor Necrosis Factor - genetics</subject><subject>Receptors, Tumor Necrosis Factor, Type I</subject><subject>Repressor Proteins</subject><subject>Signal Transduction</subject><subject>STAT3 Transcription Factor</subject><subject>Suppressor of Cytokine Signaling 3 Protein</subject><subject>Suppressor of Cytokine Signaling Proteins</subject><subject>Trans-Activators - metabolism</subject><subject>Transcription Factors</subject><subject>Tumor Necrosis Factor-alpha - immunology</subject><issn>0021-9738</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2001</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpVkEtPwzAQhH0A0VKQ-AUoJ8Ql4FcS-8ABVQWKKnGBs-W4m-KS2sFOKvrvSR_icRqN9pvd1SB0QfANIQW9XRpLiMiLIzTEmJJUFkwM0GmMS4wJ5xk_QQNCWJFxIoZoOvlqAsRovUt8lcSu2Vkf4taaTes_rIMk2oXTtXWLZN6FrdR2DSEJsAAHQbd9_AwdV7qOcH7QEXp7mLyOn9LZy-N0fD9LDWesTTkzXEttuCQ5ZcAZNTkBKUWGy9wUlWYZMZqKMpOGm1LTrJwLySnDla5yKdgI3e33Nl25grkB1wZdqybYlQ4b5bVV_yfOvquFXyuKJe3LGKGrQz74zw5iq1Y2Gqhr7cB3URVYFJLjrAev96AJPsYA1c8NgtW2avU8nu6q7tHLvz_9goee2Tef7H2p</recordid><startdate>20010515</startdate><enddate>20010515</enddate><creator>Campbell, J S</creator><creator>Prichard, L</creator><creator>Schaper, F</creator><creator>Schmitz, J</creator><creator>Stephenson-Famy, A</creator><creator>Rosenfeld, M E</creator><creator>Argast, G M</creator><creator>Heinrich, P C</creator><creator>Fausto, N</creator><general>American Society for Clinical Investigation</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>7X8</scope><scope>5PM</scope></search><sort><creationdate>20010515</creationdate><title>Expression of suppressors of cytokine signaling during liver regeneration</title><author>Campbell, J S ; Prichard, L ; Schaper, F ; Schmitz, J ; Stephenson-Famy, A ; Rosenfeld, M E ; Argast, G M ; Heinrich, P C ; Fausto, N</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c433t-43c4a9ac491623e432c61e99850b6c7fa351ca28b59c4cba25bd894230faf6983</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2001</creationdate><topic>Animals</topic><topic>Antigens, CD - genetics</topic><topic>DNA-Binding Proteins - metabolism</topic><topic>Gene Expression Regulation</topic><topic>Hepatectomy</topic><topic>Interleukin-6 - immunology</topic><topic>Liver Regeneration - immunology</topic><topic>Mice</topic><topic>Mice, Knockout</topic><topic>Proteins - genetics</topic><topic>Receptors, Tumor Necrosis Factor - genetics</topic><topic>Receptors, Tumor Necrosis Factor, Type I</topic><topic>Repressor Proteins</topic><topic>Signal Transduction</topic><topic>STAT3 Transcription Factor</topic><topic>Suppressor of Cytokine Signaling 3 Protein</topic><topic>Suppressor of Cytokine Signaling Proteins</topic><topic>Trans-Activators - metabolism</topic><topic>Transcription Factors</topic><topic>Tumor Necrosis Factor-alpha - immunology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Campbell, J S</creatorcontrib><creatorcontrib>Prichard, L</creatorcontrib><creatorcontrib>Schaper, F</creatorcontrib><creatorcontrib>Schmitz, J</creatorcontrib><creatorcontrib>Stephenson-Famy, A</creatorcontrib><creatorcontrib>Rosenfeld, M E</creatorcontrib><creatorcontrib>Argast, G M</creatorcontrib><creatorcontrib>Heinrich, P C</creatorcontrib><creatorcontrib>Fausto, N</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>The Journal of clinical investigation</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Campbell, J S</au><au>Prichard, L</au><au>Schaper, F</au><au>Schmitz, J</au><au>Stephenson-Famy, A</au><au>Rosenfeld, M E</au><au>Argast, G M</au><au>Heinrich, P C</au><au>Fausto, N</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Expression of suppressors of cytokine signaling during liver regeneration</atitle><jtitle>The Journal of clinical investigation</jtitle><addtitle>J Clin Invest</addtitle><date>2001-05-15</date><risdate>2001</risdate><volume>107</volume><issue>10</issue><spage>1285</spage><epage>1292</epage><pages>1285-1292</pages><issn>0021-9738</issn><abstract>The cytokines TNF and IL-6 play a critical role early in liver regeneration following partial hepatectomy (PH). Since IL-6 activates signal transducers and activators of transcription (STATs), we examined whether the suppressors of cytokine signaling (SOCS) may be involved in terminating IL-6 signaling. We show here that SOCS-3 mRNA is induced 40-fold 2 hours after surgery. SOCS-2 and CIS mRNA are only weakly induced, and SOCS-1 is not detectable. SOCS-3 induction after PH is transient and correlates with a decrease in STAT-3 DNA binding and a loss of tyrosine 705 phosphorylation. This response is markedly reduced in IL-6 knockout (KO) mice. TNF injection induces SOCS-3 mRNA in wild-type mice (albeit weakly compared with the increase observed after PH) but not in TNF receptor 1 or IL-6 KO mice. In contrast, IL-6 injection induces SOCS-3 in these animals, demonstrating a requirement for IL-6 in SOCS-3 induction. IL-6 injection into wild-type mice also induces SOCS-1, -2, and CIS mRNA, in addition to SOCS-3. 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| source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central; Alma/SFX Local Collection |
| subjects | Animals Antigens, CD - genetics DNA-Binding Proteins - metabolism Gene Expression Regulation Hepatectomy Interleukin-6 - immunology Liver Regeneration - immunology Mice Mice, Knockout Proteins - genetics Receptors, Tumor Necrosis Factor - genetics Receptors, Tumor Necrosis Factor, Type I Repressor Proteins Signal Transduction STAT3 Transcription Factor Suppressor of Cytokine Signaling 3 Protein Suppressor of Cytokine Signaling Proteins Trans-Activators - metabolism Transcription Factors Tumor Necrosis Factor-alpha - immunology |
| title | Expression of suppressors of cytokine signaling during liver regeneration |
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