Connexin43 Is Required for the Effective Activation of Spleen Cells and Immunoglobulin Production
Gap junctions (Gjs), formed by specific protein termed connexins (Cxs), regulate many important cellular processes in cellular immunity. However, little is known about their effects on humoral immunity. Here we tested whether and how Gj protein connexin43 (Cx43) affected antibody production in splee...
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| Veröffentlicht in: | International journal of molecular sciences 2019-11, Vol.20 (22), p.5789 |
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| creator | Huang, Yanru Mao, Zhimin Zhang, Xiling Yang, Xiawen Sawada, Norifumi Takeda, Masayuki Yao, Jian |
| description | Gap junctions (Gjs), formed by specific protein termed connexins (Cxs), regulate many important cellular processes in cellular immunity. However, little is known about their effects on humoral immunity. Here we tested whether and how Gj protein connexin43 (Cx43) affected antibody production in spleen cells. Detection of IgG in mouse tissues and serum revealed that wild-type (Cx43
) mouse had a significantly higher level of IgG than Cx43 heterozygous (Cx43
) mouse. Consistently, spleen cells from Cx43
mouse produced more IgG under both basal and lipopolysaccharide (LPS)-stimulated conditions. Further analysis showed that LPS induced a more dramatic activation of ERK and cell proliferation in Cx43
spleen cells, which was associated with a higher pro-oxidative state, as indicated by the increased NADPH oxidase 2 (NOX2), TXNIP, p38 activation and protein carbonylation. In support of a role of the oxidative state in the control of lymphocyte activation, exposure of spleen cells to exogenous superoxide induced Cx43 expression, p38 activation and IgG production. On the contrary, inhibition of NOX attenuated the effects of LPS. Collectively, our study characterized Cx43 as a novel molecule involved in the control of spleen cell activation and IgG production. Targeting Cx43 could be developed to treat certain antibody-related immune diseases. |
| doi_str_mv | 10.3390/ijms20225789 |
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| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_6888161</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2317587686</sourcerecordid><originalsourceid>FETCH-LOGICAL-c478t-1a9aa4ddb9ea7d57f8b9db5a508ed5bd8fb1955b3da1bff3151c049706ce55d93</originalsourceid><addsrcrecordid>eNpdkUtrGzEUhUVoyavZZV0E3WRRt3qMZqRNwRg3NQQS-lgLaXSVyMxIjjQTkn-fMXGCm9W9cD8O95yD0Dkl3zhX5HtY94URxkQj1QE6phVjM0Lq5sPefoROSlkTwjgT6hAdcdoIRhQ5RmaRYoTHECuOVwX_hvsxZHDYp4yHO8BL76EdwgPg-XaYIaSIk8d_Nh1AxAvouoJNdHjV92NMt12yYxcivsnJje2W_oQ-etMVONvNU_Tv5_Lv4tfs6vpytZhfzdqqkcOMGmVM5ZxVYBonGi-tclYYQSQ4YZ30liohLHeGWu85FbQllWpI3YIQTvFT9ONFdzPaHlwLccim05scepOfdDJB_3-J4U7fpgddSylpTSeBi51ATvcjlEH3obSTQRMhjUWzbWqyqWU9oV_eoes05jjZmyg-hVxVvJqory9Um1MpGfzbM5TobXd6v7sJ_7xv4A1-LYs_AwlMlvk</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2333254434</pqid></control><display><type>article</type><title>Connexin43 Is Required for the Effective Activation of Spleen Cells and Immunoglobulin Production</title><source>MEDLINE</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>MDPI - Multidisciplinary Digital Publishing Institute</source><source>PubMed Central</source><creator>Huang, Yanru ; Mao, Zhimin ; Zhang, Xiling ; Yang, Xiawen ; Sawada, Norifumi ; Takeda, Masayuki ; Yao, Jian</creator><creatorcontrib>Huang, Yanru ; Mao, Zhimin ; Zhang, Xiling ; Yang, Xiawen ; Sawada, Norifumi ; Takeda, Masayuki ; Yao, Jian</creatorcontrib><description>Gap junctions (Gjs), formed by specific protein termed connexins (Cxs), regulate many important cellular processes in cellular immunity. However, little is known about their effects on humoral immunity. Here we tested whether and how Gj protein connexin43 (Cx43) affected antibody production in spleen cells. Detection of IgG in mouse tissues and serum revealed that wild-type (Cx43
) mouse had a significantly higher level of IgG than Cx43 heterozygous (Cx43
) mouse. Consistently, spleen cells from Cx43
mouse produced more IgG under both basal and lipopolysaccharide (LPS)-stimulated conditions. Further analysis showed that LPS induced a more dramatic activation of ERK and cell proliferation in Cx43
spleen cells, which was associated with a higher pro-oxidative state, as indicated by the increased NADPH oxidase 2 (NOX2), TXNIP, p38 activation and protein carbonylation. In support of a role of the oxidative state in the control of lymphocyte activation, exposure of spleen cells to exogenous superoxide induced Cx43 expression, p38 activation and IgG production. On the contrary, inhibition of NOX attenuated the effects of LPS. Collectively, our study characterized Cx43 as a novel molecule involved in the control of spleen cell activation and IgG production. Targeting Cx43 could be developed to treat certain antibody-related immune diseases.</description><identifier>ISSN: 1422-0067</identifier><identifier>ISSN: 1661-6596</identifier><identifier>EISSN: 1422-0067</identifier><identifier>DOI: 10.3390/ijms20225789</identifier><identifier>PMID: 31752090</identifier><language>eng</language><publisher>Switzerland: MDPI AG</publisher><subject>Animals ; Antigen presentation ; Carrier Proteins - metabolism ; Cell activation ; Cell adhesion & migration ; Cell growth ; Cell Proliferation - drug effects ; Cells, Cultured ; Connexin 43 ; Connexin 43 - metabolism ; Cytokines ; Immune system ; Immunoglobulin G ; Immunoglobulin G - blood ; Immunoglobulin G - metabolism ; Immunoglobulins ; Kinases ; Lipopolysaccharides ; Lipopolysaccharides - adverse effects ; Lymphocytes ; MAP Kinase Signaling System - drug effects ; Menadione ; Mice ; Molecular weight ; NADPH Oxidase 2 - metabolism ; Organic chemistry ; Oxidative Stress ; Protein Carbonylation ; Proteins ; Spleen ; Spleen - cytology ; Spleen - immunology ; Superoxide ; Thioredoxins - metabolism</subject><ispartof>International journal of molecular sciences, 2019-11, Vol.20 (22), p.5789</ispartof><rights>2019. This work is licensed under http://creativecommons.org/licenses/by/3.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2019 by the authors. 2019</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c478t-1a9aa4ddb9ea7d57f8b9db5a508ed5bd8fb1955b3da1bff3151c049706ce55d93</citedby><cites>FETCH-LOGICAL-c478t-1a9aa4ddb9ea7d57f8b9db5a508ed5bd8fb1955b3da1bff3151c049706ce55d93</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/PMC6888161/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6888161/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,881,27903,27904,53769,53771</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31752090$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Huang, Yanru</creatorcontrib><creatorcontrib>Mao, Zhimin</creatorcontrib><creatorcontrib>Zhang, Xiling</creatorcontrib><creatorcontrib>Yang, Xiawen</creatorcontrib><creatorcontrib>Sawada, Norifumi</creatorcontrib><creatorcontrib>Takeda, Masayuki</creatorcontrib><creatorcontrib>Yao, Jian</creatorcontrib><title>Connexin43 Is Required for the Effective Activation of Spleen Cells and Immunoglobulin Production</title><title>International journal of molecular sciences</title><addtitle>Int J Mol Sci</addtitle><description>Gap junctions (Gjs), formed by specific protein termed connexins (Cxs), regulate many important cellular processes in cellular immunity. However, little is known about their effects on humoral immunity. Here we tested whether and how Gj protein connexin43 (Cx43) affected antibody production in spleen cells. Detection of IgG in mouse tissues and serum revealed that wild-type (Cx43
) mouse had a significantly higher level of IgG than Cx43 heterozygous (Cx43
) mouse. Consistently, spleen cells from Cx43
mouse produced more IgG under both basal and lipopolysaccharide (LPS)-stimulated conditions. Further analysis showed that LPS induced a more dramatic activation of ERK and cell proliferation in Cx43
spleen cells, which was associated with a higher pro-oxidative state, as indicated by the increased NADPH oxidase 2 (NOX2), TXNIP, p38 activation and protein carbonylation. In support of a role of the oxidative state in the control of lymphocyte activation, exposure of spleen cells to exogenous superoxide induced Cx43 expression, p38 activation and IgG production. On the contrary, inhibition of NOX attenuated the effects of LPS. Collectively, our study characterized Cx43 as a novel molecule involved in the control of spleen cell activation and IgG production. Targeting Cx43 could be developed to treat certain antibody-related immune diseases.</description><subject>Animals</subject><subject>Antigen presentation</subject><subject>Carrier Proteins - metabolism</subject><subject>Cell activation</subject><subject>Cell adhesion & migration</subject><subject>Cell growth</subject><subject>Cell Proliferation - drug effects</subject><subject>Cells, Cultured</subject><subject>Connexin 43</subject><subject>Connexin 43 - metabolism</subject><subject>Cytokines</subject><subject>Immune system</subject><subject>Immunoglobulin G</subject><subject>Immunoglobulin G - blood</subject><subject>Immunoglobulin G - metabolism</subject><subject>Immunoglobulins</subject><subject>Kinases</subject><subject>Lipopolysaccharides</subject><subject>Lipopolysaccharides - adverse effects</subject><subject>Lymphocytes</subject><subject>MAP Kinase Signaling System - drug effects</subject><subject>Menadione</subject><subject>Mice</subject><subject>Molecular weight</subject><subject>NADPH Oxidase 2 - metabolism</subject><subject>Organic chemistry</subject><subject>Oxidative Stress</subject><subject>Protein Carbonylation</subject><subject>Proteins</subject><subject>Spleen</subject><subject>Spleen - cytology</subject><subject>Spleen - immunology</subject><subject>Superoxide</subject><subject>Thioredoxins - metabolism</subject><issn>1422-0067</issn><issn>1661-6596</issn><issn>1422-0067</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>8G5</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNpdkUtrGzEUhUVoyavZZV0E3WRRt3qMZqRNwRg3NQQS-lgLaXSVyMxIjjQTkn-fMXGCm9W9cD8O95yD0Dkl3zhX5HtY94URxkQj1QE6phVjM0Lq5sPefoROSlkTwjgT6hAdcdoIRhQ5RmaRYoTHECuOVwX_hvsxZHDYp4yHO8BL76EdwgPg-XaYIaSIk8d_Nh1AxAvouoJNdHjV92NMt12yYxcivsnJje2W_oQ-etMVONvNU_Tv5_Lv4tfs6vpytZhfzdqqkcOMGmVM5ZxVYBonGi-tclYYQSQ4YZ30liohLHeGWu85FbQllWpI3YIQTvFT9ONFdzPaHlwLccim05scepOfdDJB_3-J4U7fpgddSylpTSeBi51ATvcjlEH3obSTQRMhjUWzbWqyqWU9oV_eoes05jjZmyg-hVxVvJqory9Um1MpGfzbM5TobXd6v7sJ_7xv4A1-LYs_AwlMlvk</recordid><startdate>20191118</startdate><enddate>20191118</enddate><creator>Huang, Yanru</creator><creator>Mao, Zhimin</creator><creator>Zhang, Xiling</creator><creator>Yang, Xiawen</creator><creator>Sawada, Norifumi</creator><creator>Takeda, Masayuki</creator><creator>Yao, Jian</creator><general>MDPI AG</general><general>MDPI</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>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>M2O</scope><scope>MBDVC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20191118</creationdate><title>Connexin43 Is Required for the Effective Activation of Spleen Cells and Immunoglobulin Production</title><author>Huang, Yanru ; Mao, Zhimin ; Zhang, Xiling ; Yang, Xiawen ; Sawada, Norifumi ; Takeda, Masayuki ; Yao, Jian</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c478t-1a9aa4ddb9ea7d57f8b9db5a508ed5bd8fb1955b3da1bff3151c049706ce55d93</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>Animals</topic><topic>Antigen presentation</topic><topic>Carrier Proteins - metabolism</topic><topic>Cell activation</topic><topic>Cell adhesion & migration</topic><topic>Cell growth</topic><topic>Cell Proliferation - drug effects</topic><topic>Cells, Cultured</topic><topic>Connexin 43</topic><topic>Connexin 43 - metabolism</topic><topic>Cytokines</topic><topic>Immune system</topic><topic>Immunoglobulin G</topic><topic>Immunoglobulin G - blood</topic><topic>Immunoglobulin G - metabolism</topic><topic>Immunoglobulins</topic><topic>Kinases</topic><topic>Lipopolysaccharides</topic><topic>Lipopolysaccharides - adverse effects</topic><topic>Lymphocytes</topic><topic>MAP Kinase Signaling System - drug effects</topic><topic>Menadione</topic><topic>Mice</topic><topic>Molecular weight</topic><topic>NADPH Oxidase 2 - metabolism</topic><topic>Organic chemistry</topic><topic>Oxidative Stress</topic><topic>Protein Carbonylation</topic><topic>Proteins</topic><topic>Spleen</topic><topic>Spleen - cytology</topic><topic>Spleen - immunology</topic><topic>Superoxide</topic><topic>Thioredoxins - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Huang, Yanru</creatorcontrib><creatorcontrib>Mao, Zhimin</creatorcontrib><creatorcontrib>Zhang, Xiling</creatorcontrib><creatorcontrib>Yang, Xiawen</creatorcontrib><creatorcontrib>Sawada, Norifumi</creatorcontrib><creatorcontrib>Takeda, Masayuki</creatorcontrib><creatorcontrib>Yao, Jian</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>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Research Library (Alumni Edition)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>Research Library Prep</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Research Library</collection><collection>Research Library (Corporate)</collection><collection>Publicly Available Content Database</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>ProQuest Central Basic</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>International journal of molecular sciences</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Huang, Yanru</au><au>Mao, Zhimin</au><au>Zhang, Xiling</au><au>Yang, Xiawen</au><au>Sawada, Norifumi</au><au>Takeda, Masayuki</au><au>Yao, Jian</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Connexin43 Is Required for the Effective Activation of Spleen Cells and Immunoglobulin Production</atitle><jtitle>International journal of molecular sciences</jtitle><addtitle>Int J Mol Sci</addtitle><date>2019-11-18</date><risdate>2019</risdate><volume>20</volume><issue>22</issue><spage>5789</spage><pages>5789-</pages><issn>1422-0067</issn><issn>1661-6596</issn><eissn>1422-0067</eissn><abstract>Gap junctions (Gjs), formed by specific protein termed connexins (Cxs), regulate many important cellular processes in cellular immunity. However, little is known about their effects on humoral immunity. Here we tested whether and how Gj protein connexin43 (Cx43) affected antibody production in spleen cells. Detection of IgG in mouse tissues and serum revealed that wild-type (Cx43
) mouse had a significantly higher level of IgG than Cx43 heterozygous (Cx43
) mouse. Consistently, spleen cells from Cx43
mouse produced more IgG under both basal and lipopolysaccharide (LPS)-stimulated conditions. Further analysis showed that LPS induced a more dramatic activation of ERK and cell proliferation in Cx43
spleen cells, which was associated with a higher pro-oxidative state, as indicated by the increased NADPH oxidase 2 (NOX2), TXNIP, p38 activation and protein carbonylation. In support of a role of the oxidative state in the control of lymphocyte activation, exposure of spleen cells to exogenous superoxide induced Cx43 expression, p38 activation and IgG production. On the contrary, inhibition of NOX attenuated the effects of LPS. Collectively, our study characterized Cx43 as a novel molecule involved in the control of spleen cell activation and IgG production. Targeting Cx43 could be developed to treat certain antibody-related immune diseases.</abstract><cop>Switzerland</cop><pub>MDPI AG</pub><pmid>31752090</pmid><doi>10.3390/ijms20225789</doi><oa>free_for_read</oa></addata></record> |
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| subjects | Animals Antigen presentation Carrier Proteins - metabolism Cell activation Cell adhesion & migration Cell growth Cell Proliferation - drug effects Cells, Cultured Connexin 43 Connexin 43 - metabolism Cytokines Immune system Immunoglobulin G Immunoglobulin G - blood Immunoglobulin G - metabolism Immunoglobulins Kinases Lipopolysaccharides Lipopolysaccharides - adverse effects Lymphocytes MAP Kinase Signaling System - drug effects Menadione Mice Molecular weight NADPH Oxidase 2 - metabolism Organic chemistry Oxidative Stress Protein Carbonylation Proteins Spleen Spleen - cytology Spleen - immunology Superoxide Thioredoxins - metabolism |
| title | Connexin43 Is Required for the Effective Activation of Spleen Cells and Immunoglobulin Production |
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